Focal Adhesion Kinase 1
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
Focal Adhesion Protein-Tyrosine Kinases
An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.
Cell Adhesion Molecules
Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.
Focal Adhesion Kinase 2
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Crk-Associated Substrate Protein
Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Vascular Cell Adhesion Molecule-1
Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154)
Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.
Intercellular Adhesion Molecule-1
Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Neural Cell Adhesion Molecules
Cell adhesion molecule involved in a diverse range of contact-mediated interactions among neurons, astrocytes, oligodendrocytes, and myotubes. It is widely but transiently expressed in many tissues early in embryogenesis. Four main isoforms exist, including CD56; (ANTIGENS, CD56); but there are many other variants resulting from alternative splicing and post-translational modifications. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, pp115-119)
Retinoblastoma-Like Protein p130
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. RBL2 contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and E2F5 TRANSCRIPTION FACTOR. RBL2 also interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
MAP Kinase Signaling System
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proto-Oncogene Proteins pp60(c-src)
Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.
Cell Adhesion Molecules, Neuronal
Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.
Amino Acid Sequence
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Mitogen-Activated Protein Kinase 1
Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.
rhoA GTP-Binding Protein
Calcium-Calmodulin-Dependent Protein Kinases
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Protein Kinase C
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
rho GTP-Binding Proteins
Recombinant Fusion Proteins
RNA, Small Interfering
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
Extracellular Signal-Regulated MAP Kinases
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Mitogen-Activated Protein Kinases
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Tumor Cells, Cultured
Mitogen-Activated Protein Kinase 3
Neural Cell Adhesion Molecule L1
A member of the immunoglobulin superfamily of neuronal cell adhesion molecules that is required for proper nervous system development. Neural cell adhesion molecule L1 consists of six Ig domains, five fibronectin domains, a transmembrane region and an intracellular domain. Two splicing variants are known: a neuronal form that contains a four-amino acid RSLE sequence in the cytoplasmic domain, and a non-neuronal form that lacks the RSLE sequence. Mutations in the L1 gene result in L1 disease. Neural cell adhesion molecule L1 is predominantly expressed during development in neurons and Schwann cells; involved in cell adhesion, neuronal migration, axonal growth and pathfinding, and myelination.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
Integrin beta Chains
Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.
p38 Mitogen-Activated Protein Kinases
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Proto-Oncogene Proteins c-akt
src Homology Domains
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
An integrin that binds to a variety of plasma and extracellular matrix proteins containing the conserved RGD amino acid sequence and modulates cell adhesion. Integrin alphavbeta3 is highly expressed in OSTEOCLASTS where it may play role in BONE RESORPTION. It is also abundant in vascular smooth muscle and endothelial cells, and in some tumor cells, where it is involved in angiogenesis and cell migration. Although often referred to as the vitronectin receptor there is more than one receptor for vitronectin (RECEPTORS, VITRONECTIN).
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Proto-Oncogene Proteins c-crk
Adaptor Proteins, Signal Transducing
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
JNK Mitogen-Activated Protein Kinases
rac1 GTP-Binding Protein
A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 188.8.131.52.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
LIM Domain Proteins
A large class of structurally-related proteins that contain one or more LIM zinc finger domains. Many of the proteins in this class are involved in intracellular signaling processes and mediate their effects via LIM domain protein-protein interactions. The name LIM is derived from the first three proteins in which the motif was found: LIN-11, Isl1 and Mec-3.
A fungal metabolite that blocks cytoplasmic cleavage by blocking formation of contractile microfilament structures resulting in multinucleated cell formation, reversible inhibition of cell movement, and the induction of cellular extrusion. Additional reported effects include the inhibition of actin polymerization, DNA synthesis, sperm motility, glucose transport, thyroid secretion, and growth hormone release.
Intracellular Signaling Peptides and Proteins
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Gene Expression Regulation
Specific cell surface receptors which bind to FIBRONECTINS. Studies have shown that these receptors function in certain types of adhesive contact as well as playing a major role in matrix assembly. These receptors include the traditional fibronectin receptor, also called INTEGRIN ALPHA5BETA1 and several other integrins.
NIH 3T3 Cells
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Mitogen-Activated Protein Kinase Kinases
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
An alpha integrin with a molecular weight of 160-kDa that is found in a variety of cell types. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds. Integrin alphaV can combine with several different beta subunits to form heterodimers that generally bind to RGD sequence-containing extracellular matrix proteins.
Extracellular Matrix Proteins
Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).
Dose-Response Relationship, Drug
Receptor Protein-Tyrosine Kinases
Cyclic AMP-Dependent Protein Kinases
Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.
Sequence Homology, Amino Acid
Proto-Oncogene Proteins c-fyn
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.
Activated-Leukocyte Cell Adhesion Molecule
Phosphotransferases (Alcohol Group Acceptor)
rac GTP-Binding Proteins
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Anchoring points where the CYTOSKELETON of neighboring cells are connected to each other. They are composed of specialized areas of the plasma membrane where bundles of the ACTIN CYTOSKELETON attach to the membrane through the transmembrane linkers, CADHERINS, which in turn attach through their extracellular domains to cadherins in the neighboring cell membranes. In sheets of cells, they form into adhesion belts (zonula adherens) that go all the way around a cell.
cdc42 GTP-Binding Protein
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Reverse Transcriptase Polymerase Chain Reaction
Lymphocyte Function-Associated Antigen-1
An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.
Gene Expression Regulation, Enzymologic
Green Fluorescent Proteins
Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792)
Protein Kinase C-alpha
Receptors, Cell Surface
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Gene Knockdown Techniques
Proto-Oncogene Proteins c-yes
Cell Line, Transformed
Amino Acid Motifs
Protein Tyrosine Phosphatases
GRB2 Adaptor Protein
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
Heterocyclic Compounds, Bridged-Ring
"The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to ... "Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration". J. Cell Biol. 140 (1): 211-21. doi: ... "The Fes protein-tyrosine kinase phosphorylates a subset of macrophage proteins that are involved in cell adhesion and cell-cell ... associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae". Mol. Cell. Biol. 16 (7): ...
"The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to ... "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". J. Biol. Chem. ... Avraham S, Avraham H (1997). "Characterization of the novel focal adhesion kinase RAFTK in hematopoietic cells". Leuk. Lymphoma ... "Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol ...
Adapter molecule crk
1994). "Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src". Mol. Cell. Biol ... 1996). "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane". Mol. Cell. Biol ... "Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src ... "Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts". J. Cell ...
The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). ... "Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration". The ... Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of ... Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of ...
"Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains". The Journal of Cell Biology. ... a new focal adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion". The Journal of Cell Biology ... a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase". ... The proteins that bind to paxillin are diverse and include protein tyrosine kinases, such as Src and focal adhesion kinase (FAK ...
2003). "Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha 5/alpha 6-triangle of protein phosphatase-1 ... Cell. Biol. 21 (20): 6841-50. doi:10.1128/MCB.21.20.6841-6850.2001. ISSN 0270-7306. PMC 99861. PMID 11564868. Morimoto, ... Tan I, Ng CH, Lim L, Leung T (2001). "Phosphorylation of a novel myosin binding subunit of protein phosphatase 1 reveals a ... Kawabe T, Muslin AJ, Korsmeyer SJ (1997). "HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell- ...
... a new focal adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion". J. Cell Biol. 151 (7): 1435- ... "A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading". J. Cell ... a 42 kDa focal adhesion protein, related to the alpha-actinin superfamily". J Cell Sci. 114 (Pt 3): 525-38. PMID 11171322. " ... Zhang Y, Chen K, Tu Y, Wu C (2004). "Distinct roles of two structurally closely related focal adhesion proteins, alpha-parvins ...
Shofuda T, Shofuda K, Ferri N (2004). "Cleavage of focal adhesion kinase in vascular smooth muscle cells overexpressing ... "Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2". Cancer Cell. 6 (3): 251-61. ... This gene produces at least two transcripts, one which encodes a membrane-bound form and another a soluble form of the protein ... proteolysis in malignant cells". J. Biol. Chem. 279 (6): 4260-8. doi:10.1074/jbc.M311569200. PMID 14645246. Lang R, Braun M, ...
"Differential regulation of Pyk2 and focal adhesion kinase (FAK). The C-terminal domain of FAK confers response to cell adhesion ... "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins". ... Chen HC, Appeddu PA, Parsons JT, Hildebrand JD, Schaller MD, Guan JL (Jul 1995). "Interaction of focal adhesion kinase with ... and to focal adhesions in smooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage ...
protein tyrosine kinase binding. Cellular component. • cytoplasm. • cell junction. • cytoskeleton. • focal adhesion. • cell ... cell adhesion. • positive regulation of cell migration. • positive regulation of protein tyrosine kinase activity. • positive ... "Dcas supports cell polarization and cell-cell adhesion complexes in development". PLOS ONE. 5 (8): e12369. Bibcode:2010PLoSO... ... These include association with FAK and Src family kinases at focal adhesions to transmit integrin-initiated signals to ...
Deleted in Colorectal Cancer
"Focal adhesion kinase in netrin-1 signaling". Nat. Neurosci. 7 (11): 1204-12. doi:10.1038/nn1330. PMID 15494733. S2CID 2901216 ... and C-terminal sequences regulate oligomerization and binding to target proteins". Mol. Cell. Biol. 19 (1): 724-32. doi:10.1128 ... DCC induces cell death on epithelial cells when no netrin-1 is bound. Besides from loss of heterozygosity of DCC, this ... The division of these cells occurs at the base of villi, and cells are pushed upwards by subsequent divisions to the tip where ...
"The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions". Molecular Cell ... "A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading". The Journal ... OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". ... binding to paxillin LD1 motif regulates ILK localization to focal adhesions". The Journal of Biological Chemistry. 276 (26): ...
... and activating focal adhesion kinase (FAK). FAK has been shown to promote the inhibition of cell proliferation and cell ... Another proposed mechanism of action is that angiostatin is able to reduce epithelial cell migration by binding to avB3- ... Angiostatin is known to bind many proteins, especially to angiomotin and endothelial cell surface ATP synthase but also ... not only inhibits ATP production in tumor cells but also inhibits the cell's ability to maintain the acidic pH of tumor cells. ...
... and regulates focal adhesion kinase (pp125(FAK))". Cell Biology International. 26 (6): 567-71. doi:10.1006/cbir.2002.0900. PMID ... 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". ... "CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line". The Journal of ... "HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias". ...
Receptor insulinu sličnog faktora rasta 1
"Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility". Mol. Cell. Biol. ( ... "Localization of the insulin-like growth factor I receptor binding sites for the SH2 domain proteins p85, Syp, and GTPase ... in tongue squamous cell carcinoma cells". Biochemical Journal 432 (1): 199-205. PMID 20819078. doi:10.1042/BJ20100859. ... "J. Cell Biol. (United States) 155 (5): 809-20. ISSN 0021-9525. PMC 2150867. PMID 11724822. doi:10.1083/jcb.200106139. Cite uses ...
"Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". The Journal of ... binds to the focal adhesion adaptor proteins paxillin and Hic-5". The Journal of Biological Chemistry. 277 (14): 12270-4. doi: ... with focal adhesion kinase". The Journal of Biological Chemistry. 273 (41): 26516-21. doi:10.1074/jbc.273.41.26516. PMID ... which localizes to both focal adhesions and the nuclear matrix". Molecular Biology of the Cell. 11 (6): 2007-18. doi:10.1091/ ...
Focal adhesion targeting region
"The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin". Nat. Struct. ... Focal adhesions form and dissipate as cells attach and detach from matrix during cell adhesion and cell migration. The FAK ... the focal adhesion targeting domain is a conserved protein domain that was first identified in focal adhesion kinase (FAK), ... are also found in other proteins that localize to paxillin-containing focal adhesions and are involved in cell adhesion and ...
It also regulates the actin cytoskeleton, cell adhesion, and cell migration. Syndecan-4 activates protein kinase C (PKC), an ... "Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component". Mol Biol Cell. 5 (2 ... "Human CASK/LIN-2 Binds Syndecan-2 and Protein 4.1 and Localizes to the Basolateral Membrane of Epithelial Cells". J. Cell Biol ... Woods A, Couchman JR (May 1998). "Syndecans: synergistic activators of cell adhesion". Trends Cell Biol. 8 (5): 189-92. doi: ...
"Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". J. Biol. Chem. 276 (25): 23092-6. ... and Cdc42-Activated Lim-Kinase 2". J. Cell Biol. 147 (7): 1519-32. doi:10.1083/jcb.147.7.1519. PMC 2174243. PMID 10613909. ... "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895-8. doi: ... "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895-8. doi: ...
"Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains". The Journal of Cell Biology. ... a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase". ... PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their ... tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells". ...
Rho kinase inhibitor
... cell migration, and maintenance of cell viability and morphology, in part by regulating stress fibers and focal adhesions. ... and blocking RhoA binding to ROCK. Some studies suggest that Rho kinase inhibitors also play a role in anti-angiogenesis by ... kinases without affecting activity of PAK1 and DMPK at 5 μM concentrations in in vitro cell-free kinase activity assays. DJ4 ... although studies have shown mixed results for other cells types. Molecular Mechanism: Rho kinase inhibitors act on Rho kinase ...
... adaptor protein causes Src-dependent cell spreading and activation of focal adhesion kinase in murine brain endothelial cells ... Diakonova M, Gunter DR, Herrington J, Carter-Su C (Mar 2002). "SH2-Bbeta is a Rac-binding protein that regulates cell motility ... cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells ... cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells ...
... and protein-tyrosine phosphatase 1B coregulate the disassembly of the focal adhesion kinase x Src complex and promote cell ... Upon substrate binding, PTP1B undergoes a structural modification in which the WPD loop closes around the substrate, ... Janus kinase 2, TYK2, and focal adhesion kinase as well as other tyrosine-phosphorylated proteins, including BCAR1, DOK1, beta- ... Cell. 117 (6): 699-711. doi:10.1016/j.cell.2004.05.018. PMID 15186772. S2CID 18072568. Mahadev K, Zilbering A, Zhu L, Goldstein ...
Src and focal adhesion kinase to stimulate c-Jun N-terminal kinases in transfected COS-7 cells and human monocytic THP-1 cells ... The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind opioid-like compounds in the brain and ... These include extracellular signal-regulated kinase, p38 mitogen-activated protein kinases, and c-Jun N-terminal kinases. The ... "Mitogenic signaling via endogenous kappa-opioid receptors in C6 glioma cells: evidence for the involvement of protein kinase C ...
Tropic cues involved in growth cone guidance
... protein kinase focal adhesion kinase (FAK) and MAP Kinase (MAPK) have been implicated in mediating downstream attractive ... One example is the Ig cell-adhesion molecule (IgCAM) family; this family of adhesion molecules are suggested to interact with ... Upon binding Semaphorins, the Npn1 receptor transmits signaling to adjacent surface molecules, known as Plexins; this is ... a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases". Cell. 82 (3): 359-70. doi:10.1016/0092-8674(95) ...
Cyclin-dependent kinase 5
Cdk5 also phosphorylates Focal adhesion kinase (FAK). This may stimulate nuclear translocation, which plays an important role ... making kinases an essential part of the cell due to their role in the metabolism, cell signaling and many other processes. Cdk5 ... The gene CABLES1 codes for a cyclin-dependent kinase binding protein, whose complete name is Cdk5 and Abl enzyme substrate 1. ... Therefore, this kinase promotes T-cell survival and motility. Cdk5 also takes part in the production of interleukin 2 (IL-2), a ...
Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins. Janus tyrosine ... of cell-cell contacts. Filopodin, a slime mould protein that binds actin and which is involved in the control of cell motility ... is involved in the binding of the barbed end of actin filaments to the plasma membrane in the undercoat of the cell-to-cell ... Aside from binding to membranes, the activated FERM domain of ERM proteins can also bind the guanine nucleotide dissociation ...
"Regulation of human endothelial cell focal adhesion sites and migration by cGMP-dependent protein kinase I". J. Biol. Chem. 275 ... N-terminal EVH1 domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions cell ... 1994). "cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated ... and characterization of a zyxin-related protein that binds the focal adhesion and microfilament protein VASP (vasodilator- ...
"Nck-2 interacts with focal adhesion kinase and modulates cell motility". Int. J. Biochem. Cell Biol. 34 (7): 791-805. doi: ... Su YC, Han J, Xu S, Cobb M, Skolnik EY (March 1997). "NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates ... Su YC, Han J, Xu S, Cobb M, Skolnik EY (1997). "NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the ... Ren R, Ye ZS, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding ...
Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis
... and its ability to bind the tight junction prote … ... Trop-2 has been suggested to regulate cell-cell adhesion, given ... its high homology with the other member of the Trop family, Trop-1/EpCAM, ... Epithelial Cell Adhesion Molecule * Fibronectins / metabolism * Focal Adhesion Kinase 1 / metabolism * GTP-Binding Proteins / ... Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis J Cell Physiol. 2012 Nov;227(11 ...
Kurenova E[au] - PubMed - NCBI
Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells. ... Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines. ... Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein. ... Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial ...
Toward total synthesis of cell function: Reconstituting cell dynamics with synthetic biology | Science Signaling
... engulfment and cell motility; FAK, focal adhesion kinase; Grb-2, growth factor receptor-bound protein-2; DG, diacylglycerol; IP ... Introducing these constructs into inert cell lines, such as HeLa epithelial cells and Cos-7 fibroblast-like cells, these cells ... Wang et al. showed that Rac activation in a single cell directed the migration of border cells, a collection of 6 to 10 cells ... Stochastic ERK activation induced by noise and cell-to-cell propagation regulates cell density-dependent proliferation. Mol. ...
Dr Daniel Whitcomb - School of Clinical Sciences publications
... cell adhesion and motility via cleavage of paxillin, focal adhesion kinase and talin. Knockdown or expression of the truncated ... TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, ... TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, ... A stable TRPC6 knock out podocyte cell line was generated from TRPC6 knockout mice. These cells were engineered to express wild ...
Focal adhesion kinase is involved in mechanosensing during fibroblast migration | PNAS
... colocalizing with integrins at focal adhesions in adherent cells (3-5). The C-terminal domain contains multiple binding sites ... Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate ... Based on the apparently enlarged focal adhesions (21), and prolonged lifespan of focal adhesions during cell spreading (39), it ... The FAK-null cell failed to show a response in focal adhesions, whereas the cell expressing WT-FAK and F397-FAK responded by ...
Enhanced Recovery of Injury-Caused Downregulation of Paxillin Protein by eNOS Gene Expression in Rat Carotid Artery |...
Focal adhesion kinase and paxillin bind to peptides mimicking β-integrin cytoplasmic domains. J Cell Biol. 1995;130:1181-1187. ... focal adhesion kinase and paxillin tyrosine phosphorylation and on cell migration in rabbit aortic vascular smooth muscle cells ... 4 5 6 Paxillin can directly associate with cytosolic protein tyrosine kinases, csk, crk, c-src, and focal adhesion kinase (FAK ... Paxillin is highly expressed in smooth muscle cells (SMCs) and is localized in dense plaques in vivo and at focal adhesion ...
Studies on Focal Adhesion Kinase in human breast cancer cell MDA-MB-231
Focal Adhesion Kinase (FAK) transmits the signal, produced as a result of Integrin-ECM binding, to cell-interior. FAK is a non- ... Focal adhesion kinase: In command and control of cell motility. Nature Reviews Molecular Cell Biology, 6, 56- 68. doi:10.1038/ ... Required role of focal adhesion kinase (FAK) for integrinstimulated cell migration. Journal of Cell Sciences, 112, 2677-2691. ... Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. Journal of ...
Yersinia Outer Protein P of Yersinia enterocolitica Simultaneously Blocks the Nuclear Factor-κB Pathway and Exploits...
YopH tyrosine dephosphorylates host cell proteins, such as p130Cas and focal adhesion kinase FAK (2). By action of these Yops, ... Thereby, YopP bound and inhibited the macrophage NF-κB-activating kinase IKKβ. YopP- and Yersinia-, but not Salmonella-induced ... For assessment of cell death of transfected cells, blue transfected cells were counted, and morphology of transfected cells was ... NF-κB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc. Natl. Acad. Sci. USA 95: 3537. ...
Src-mediated coupling of focal adhesion kinase to integrin αvβ5 in vascular endothelial growth factor signaling | JCB
Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J. Cell Biol. 130:1181-1187. ... Protein kinase C αvβ5-dependent cytoskeletal associations and focal adhesion kinase phosphorylation. J. Cell Biol. 134:1323- ... tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. J. ... The cytoplasmic tyrosines of integrin subunit β1 are involved in focal adhesion kinase activation. Mol. Cell Biol. 20:5758-5765 ...
An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces | Cancer Research
... outside-in events that occur after adhesion when integrin binding induces the activation of kinases within the focal adhesion ... Focal adhesion kinase regulates metastatic adhesion of carcinoma cells within liver sinusoids. Am J Pathol 2005; 166: 585-96. ... Colon cancer cell adhesion in response to Src kinase activation and actin-cytoskeleton by non-laminar shear stress. J Cell ... Pressure activates colon cancer cell adhesion by inside-out focal adhesion complex and actin cytoskeletal signaling. ...
An Analysis of Gene Array Data Related to Cell Adhesion and Prostate Cancer | SpringerLink
First, to discover a gene, or a group of genes, related to the attachment of prostate cells to their neighboring... ... Genistein-simulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-l- ... Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. Mol ... 200 lb). Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced FAK-b-l-integrin complex formation. ...
Targeting to C-Terminal Myosin Heavy Chain May Explain Mechanotransduction Involving Focal Adhesion Kinase in Cardiac Myocytes ...
Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol. 1994; 14: ... Targeting membrane-localized focal adhesion kinase to focal adhesions: roles of tyrosine phosphorylation and SRC family kinases ... Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem. ... Costameres are also sites of integrin clusters and share a similarity to focal adhesions.11,12 Focal adhesion kinase (Fak), a ...
Changes in Na(+)-K(+)-ATPase activity influence cell attachment to fibronectin
Here we have demonstrated, using COS cells that were untransfected or transfected with wild-type rat ouabain-resistant Na(+)-K ... Ouabain reduced focal adhesion kinase autophosphorylation but had no effect on cell surface integrin expression. These results ... Calcium-Binding Proteins / antagonists & inhibitors * Cell Adhesion / drug effects * Cell Adhesion / physiology ... Changes in Na(+)-K(+)-ATPase activity influence cell attachment to fibronectin Am J Physiol Cell Physiol. 2002 Feb;282(2):C302- ...
Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells.
Cell Proliferation / drug effects. Cells, Cultured. Enzyme Inhibitors / pharmacology. Focal Adhesion Protein-Tyrosine Kinases ... EC 184.108.40.206/Mitogen-Activated Protein Kinase 3; EC 220.127.116.11/RND3 protein, human; EC 18.104.22.168/rho GTP-Binding Proteins ... EC 22.214.171.124/Focal Adhesion Protein-Tyrosine Kinases; EC 126.96.36.199/src-Family Kinases; EC 188.8.131.52/Proto-Oncogene Proteins c-akt ... of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased focal adhesion kinase ( ...
5f28 - Proteopedia, life in 3D
Tyrosine phosphorylation of growth factor receptor-bound protein-7 by focal adhesion kinase in the regulation of cell migration ... Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and ... Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion. J Biol Chem. 2001 Jun 1;276(22):19512- ... Focal adhesion kinase governs cardiac concentric hypertrophic growth by activating the AKT and mTOR pathways. J Mol Cell ...
Focal Adhesion Kinases in Adhesion Structures and Disease
"Focal adhesion kinase and paxillin bind to peptides mimicking β integrin cytoplasmic domains," The Journal of Cell Biology, vol ... "Cloning and characterization of cell adhesion kinase β, a novel protein- tyrosine kinase of the focal adhesion kinase subfamily ... "Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase," Nature Cell Biology, vol. 7, ... "Src SH2 arginine 175 is required for cell motility: specific focal adhesion kinase targeting and focal adhesion assembly ...
Simultaneous Inhibition of Focal Adhesion Kinase and Src Enhances Detachment and Apoptosis in Colon Cancer Cell Lines |...
Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol. Cell. Biol., 14: ... cells by focal adhesion kinase (FAK). Role of FAK in maintaining focal adhesion organization after acute renal cell injury. J. ... The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells. Cell Growth ... Control of adhesion-dependent cell survival by focal adhesion kinase. J. Cell Biol., 134: 793-799, 1996. ...
Monoclonal Antibody Neuron Adhesion from Cell Signaling Technology
Background: Focal adhesion kinase (FAK) is a widely expressed cytoplasmic protein tyrosine kinase involved in integrin-mediated ... which is a binding site for the Src family kinases PI3K and PLCγ (2-5). Recruitment of Src family kinases results in the ... Background: Focal adhesion kinase (FAK) is a widely expressed cytoplasmic protein tyrosine kinase involved in integrin-mediated ... Background: Focal adhesion kinase (FAK) is a widely expressed cytoplasmic protein tyrosine kinase involved in integrin-mediated ...
siRNA Extracellular Matrix Disassembly from Cell Signaling Technology
Background: Focal adhesion kinase (FAK) is a widely expressed cytoplasmic protein tyrosine kinase involved in integrin-mediated ... which is a binding site for the Src family kinases PI3K and PLCγ (2-5). Recruitment of Src family kinases results in the ... family of multidomain membrane proteins influences cell signaling and adhesion by shedding cell surface proteins such as ... Disintegrin and cysteine-rich domains mediate adhesion, at least in part, through binding to integrins. Phosphorylation of the ...
CureFAKtor Pharmaceuticals Demonstrates Novel Focal Adhesion Kinase (FAK) Inhibitor C4 Analogs Inhibited Pancreatic Cancer...
Focal,Adhesion,Kinase,(FAK),Inhibitor,C4,Analogs,Inhibited,Pancreatic,Cancer,Tumor,Growth,as,Single,Agents,medicine,advanced ... Inhibitors Targeted to Protein-Protein Binding Sites Inhibit Pancreatic Cancer Cells Growth. 3. CureFAKtor Pharmaceuticals ... About Focal Adhesion Kinase (FAK). Focal adhesion Kinase (FAK) is substantially over-expressed in many solid tumors. FAK ... CureFAKtor Pharmaceuticals is a biopharmaceutical company focused on the research and development of Focal Adhesion Kinase ...
CureFAKtor Pharmaceuticals Demonstrates that Novel Focal Adhesion Kinase (FAK) Inhibitors Decrease Pancreatic Cancer Tumor...
Focal,Adhesion,Kinase,(FAK),Inhibitors,Decrease,Pancreatic,Cancer,Tumor,Blood,Flow,and,Reduce,Blood,Vessel,Density,medicine, ... Inhibitors Targeted to Protein-Protein Binding Sites Inhibit Pancreatic Cancer Cells Growth. 2. CureFAKtor Pharmaceuticals ... About Focal Adhesion Kinase (FAK). Focal adhesion Kinase (FAK) is substantially over-expressed in many solid tumors. FAK ... CureFAKtor Pharmaceuticals is a biopharmaceutical company focused on the research and development of Focal Adhesion Kinase ...
Cell adhesion - Integrin-mediated cell adhesion and migration Pathway Map - PrimePCR | Life Science | Bio-Rad
The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase ... Focal adhesion kinase: a regulator of focal adhesion dynamics and cell movement. Oncogene 2000 Nov 20;19(49):5606-13 ... Focal adhesion kinase: a regulator of focal adhesion dynamics and cell movement. Oncogene 2000 Nov 20;19(49):5606-13 ... Focal adhesion kinase: in command and control of cell motility. Nature reviews. Molecular cell biology 2005 Jan;6(1):56-68 ...
Transglutaminase-2: a new endostatin partner in the extracellular matrix of endothelial cells | Biochemical Journal
... focal adhesion kinase; HEK, human embryonic kidney; HIF, hypoxia-inducible factor; HUVEC, human umbilical vein endothelial cell ... Inhibition experiments support the hypothesis that the GTP-binding site of TG-2 is a potential binding site for endostatin. ... Recombinant human endostatin binds to TG-2 with an affinity in the nanomolar range (Kd=6.8 nM). Enzymatic assays indicated that ... Transglutaminase-2: a new endostatin partner in the extracellular matrix of endothelial cells. Clément Faye, Antonio Inforzato ...
Types of cell junctions by caroline farid on Prezi
Binding of integrin to extra cellular matrix proteins.. Binding of focal adhesion kinase to the cytoskeleton complex ... The cadherins from adjacent cells interact to zipper up the two cells together. Inside the cell E-cadherin binds to catenin, ... A. Cell-to-cell B. Cell-to-matrix. 3.Communicating (gap) junctions Types of intercellular junctions: 1. transmembrane adhesive ... The intercellular space is very wide 30nm Cell-to-cell junctions. 2. Macula adherens (desmosome) Cell-to-matrix junctions. 1. ...
Paxillin nuclear-cytoplasmic localization is regulated by phosphorylation of the LD4 motif: evidence that nuclear paxillin...
This region overlaps an important LD4 motif that binds GIT1 and FAK1 (focal-adhesion kinase 1). We provide evidence that ... a major focal-adhesion complex component belongs to the subfamily of LIM domain proteins and participates in cell adhesion- ... focal-adhesion kinase; FCS, foetal calf serum; GFP, green fluorescent protein; GIT1, GRK (G-protein-coupled-receptor kinase)- ... It is implicated in cell-motility responses upon activation of cell-surface receptors and can recruit, among others, the GIT1 [ ...
Staurosporine induces endothelial cell apoptosis via focal adhesion kinase dephosphorylation and focal adhesion disassembly...
Regulation of the 14-3-3-binding protein p39 by growth factors and nutrients in rat PC12 pheochromocytoma cells Biochem J ( ... cell apoptosis via focal adhesion kinase dephosphorylation and focal adhesion disassembly independent of focal adhesion kinase ... cell apoptosis via focal adhesion kinase dephosphorylation and focal adhesion disassembly independent of focal adhesion kinase ... Focal adhesion kinase (FAK) is thought to play a key role in maintaining focal adhesion function and cell survival, whereas ...
Eph receptors and ephrins in cancer: bidirectional signalling and beyond. - PubMed - NCBI
EPHRIN-B1 disrupts focal adhesions through GRB4. Phosphorylation inhibits EPHRIN-B1 binding to PAR6, allowing PAR6 to bind GTP- ... The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumour blood ... EPHA2 (and EPHB2) activate RHOA through focal adhesion kinase (FAK),. EPHA4 activates signal transducer and activator of ... and inactivates focal adhesion kinase (FAK) through the SHP2 phosphatase. EPHA4 inhibits RAP1 through spine-associated RAPGAP ( ...
Cell-generated traction forces induce integrin activation resulting in focal adhesion cell - Aurora Kinases as Druggable...
Cell-generated traction forces induce integrin activation resulting in focal adhesion cell. Home / Uncategorized / Cell- ... signaling device of cell adhesion. Keywords: integrin adhesion cytoskeletal stress cell extender micropost array cell ... Cell-generated traction forces induce integrin activation resulting in focal adhesion cell. December 5, 2016. exposed0 comments ... Cell-generated traction forces induce integrin activation resulting in focal adhesion cell and growth growing. ...
Prostate apoptosis response-4 and tumor suppression: it's not just about apoptosis anymore | Cell Death & Disease
... and discuss how the interaction of Par-4 with different regulators influence cell fate. This review also highlights the new ... 6B). CEBPB is a transcriptional regulator of focal adhesion kinase (FAK), a cytoplasmic non-receptor protein tyrosine kinase ... Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. Mol. Cell 20, 33-44 (2005). ... 2A). Normal cells have relatively limited basal PKA activity when compared to cancer cells. This explains why normal cells are ...
Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro | Gut
... such as focal adhesion kinase,11 protein kinase C (PKC),8extracellular signal regulated kinase,11 12 Janus associated kinases, ... Stimulation of endogenous u-PA expression and binding by butyrate in Caco-2 cells, and EGF and PMA in LIM1215 cells, appeared ... phosphorylation of focal adhesion proteins and activation of mitogen-activated protein kinase in cultured endothelial cells. J ... 1995) Migrating vascular smooth muscle cells polarize cell surface urokinase receptors after injury in vitro. Exp Cell Res 217: ...
ProteinsProteinIntegrinsReceptorsMigrationPaxillinDownstreamRegulatesProliferationApoptosisCytoskeletonPathwaysFamily kinasesSignal TransductionIntracellularPathwayTurnoverInduceMotilityMediatesInducesActivationVitroInhibitionCytoplasmicMoleculesEpithelialPhosphatidylinositolReceptor tyrosinMembraneRegulateCellularRegulationSubstrateMetastasisVascularEmbryonicLocalizes to focalVinculinPTK2AutophosphorylationCytoskeletalStress fibersComplexesInteractionTumor cellsNovel Focal AdhesiInhibitsInhibitorDisassemblyMAPKCatalyticTyrosine-phosphorylatedLocalizationEndothelial cellFibronectinIntegrin engagementLoss of focal adhesionsNonreceptor tyrosineMoleculeMediateLigandsActivatesDifferentiation
- Trop-2 has been suggested to regulate cell-cell adhesion, given its high homology with the other member of the Trop family, Trop-1/EpCAM, and its ability to bind the tight junction proteins claudin-1 and claudin-7. (nih.gov)
- Mechanistically, we show that TRPC6 binds to ERK1/2 and the actin regulatory proteins, caldesmon and calpain 1 and 2. (bristol.ac.uk)
- The C-terminal domain contains multiple binding sites for focal adhesion proteins that associate with integrin clusters, such as paxillin, p130cas ( 6 ), and talin ( 7 , 8 ). (pnas.org)
- Phosphorylation of this site promotes the binding of FAK with the SH2 domain of Src family kinase ( 9 ) and other proteins carrying this domain, such as phospholipase C ( 10 ). (pnas.org)
- FAK transduces signal from ECM to the cell interior through a series phosphorylation and dephosphorylation of different signaling proteins. (scirp.org)
- A broad range of bacterial pathogens, including the Gram-negative bacterium Yersinia , uses a so-called type III protein secretion machinery to deliver bacterial effector proteins into the host cell for modulation of cellular functions. (jimmunol.org)
- The type III protein secretion machinery of Yersinia and a set of six effector Yersinia outer proteins (Yops) 3 (YopE, YopH, YopM, YopO/YpkA, YopP/YopJ, YopT) are encoded by a 70-kb virulence plasmid that is common to the three pathogenic Yersinia species ( 1 ). (jimmunol.org)
- Yersinia causes depolymerization of the actin microfilament structure by affecting members of the small GTP-binding proteins Rho, Rac, and Cdc42 (YopE, YopT) ( 2 ). (jimmunol.org)
- YopH tyrosine dephosphorylates host cell proteins, such as p130Cas and focal adhesion kinase FAK ( 2 ). (jimmunol.org)
- Cells swirling through the lymphatic or venous circulation or around a body cavity or surgical site contact endothelial or other cells or extracellular matrix proteins, adhering if the correct membrane receptors are deployed at the right place to bind to adhesion sites and if the energy of cell movement is not so great that it overcomes binding affinity. (aacrjournals.org)
- However, work from our laboratory ( 1 - 3 ) and others ( 4 , 5 ) suggests that cancer cells may regulate their own adhesion to matrix proteins, endothelial cells, or surgical wounds by intracellular signals that regulate the binding affinity of matrix receptors including β 1 -integrin heterodimers. (aacrjournals.org)
- 6 Human titin mutations as well as deletion of the α-actinin binding proteins such as ALP or MLP in the mouse causes dilated cardiomyopathy. (ahajournals.org)
- this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. (proteopedia.org)
- This acts as a protein-interaction motif, similar to those found in other adhesion-related proteins such as focal adhesion kinase (FAK) and vinculin. (wikipedia.org)
- Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. (hindawi.com)
- We also will highlight several important tyrosine kinases and other signaling proteins that are known to control the formation and function of these adhesion structures, and we will discuss their role in pathophysiology. (hindawi.com)
- Although focal adhesions, podosomes, and invadopodia share common signaling proteins, they are distinct in cellular architecture and function (summarized in Table 1 ). (hindawi.com)
- One of the proteins implicated in the mechanism of anoikis is focal adhesion kinase (FAK), a nonreceptor tyrosine kinase that is involved in the control of cell-extracellular interactions such as spreading, migration, motility, and survival ( 3 -5 ). (aacrjournals.org)
- External stimuli that control cell migration are transduced into intracellular biochemical signals through the interactions of transmembrane integrins that bind to the extracellular matrix (ECM) proteins [ 1 ]. (bio-rad.com)
- Most integrins recognize several ECM proteins, such as Laminin 1 , Fibronectin and Collagen ( types I, II and IV ), whereas alpha-5/beta-1 integrin recognizes only Fibronectin [ 3 ]. (bio-rad.com)
- The integrin-binding proteins Paxillin and Talin recruit Focal adhesion kinase ( FAK1 ) and a cytoskeletal protein Vinculin to focal contacts. (bio-rad.com)
- PI(4,5)P2 enhances Talin association with Integrins and stimulates the direct transient interactions of diverse cytoskeleton actin-binding proteins Vinculin , Alpha-actinin and Wiskott-Aldrich syndrome-like ( N-WASP ), thereby regulating Actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex [ 7 ], [ 10 ]. (bio-rad.com)
- Background: The ADAM (A Disintegrin and A Metalloprotease) family of multidomain membrane proteins influences cell signaling and adhesion by shedding cell surface proteins such as cytokines and growth factors, by influencing cell adhesion to the extracellular matrix (ECM), and by directly remodeling the ECM. (cellsignal.com)
- Phosphorylation of the cytoplasmic tail as well as its interaction with other signaling proteins may influence intra- and extracellular signaling (1). (cellsignal.com)
- Background: Caspase-3 (CPP-32, Apoptain, Yama, SCA-1) is a critical executioner of apoptosis, as it is either partially or totally responsible for the proteolytic cleavage of many key proteins, such as the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (1). (cellsignal.com)
- Inside the cell E-cadherin binds to catenin, which in turn binds to other proteins in a protein complex with actin filaments Desmosomes connect two cells together structure: thickening of adjacent cell membrane, a pair of attachment plaques, transemembrane protein and tonofilaments. (prezi.com)
- Binding of integrin to extra cellular matrix proteins. (prezi.com)
- Paxillin, a major focal-adhesion complex component belongs to the subfamily of LIM domain proteins and participates in cell adhesion-mediated signal transduction. (biochemj.org)
- Several adhesion proteins including zyxin, Hic5 and Trip6 are also nuclear and can exert transcriptional effects. (biochemj.org)
- The major sperm protein (MSP) domain from VAMP (vesicle-associated membrane protein)-associated protein (VAP) proteins is another Eph ligand that can compete with ephrins for binding. (nih.gov)
- 7-10 Several studies have indicated that u-PA binding activates several signalling molecules implicated in the control of cell migration, such as focal adhesion kinase, 11 protein kinase C (PKC), 8 extracellular signal regulated kinase, 11 12 Janus associated kinases, 13 14 src family tyrosine kinases, 15 and G proteins. (bmj.com)
- Tyr397 is a major autophosphorylation site in FAK and phosphorylation at Tyr397 creates a binding site for Src family kinases and Src homology 2-containing proteins, suggesting a role of Src in adhesion turnover regulation [ 3 ]. (hindawi.com)
- These heterodimeric transmembrane receptors act as bidirectional signal transducers: interactions with cytoskeletal adaptor proteins that associate with the cytoplasmic tails of integrins control the ligand-binding activity of integrins and, conversely, the extracellular ligand-binding, clustering or pulling on integrins triggers the recruitment of cytoskeletal adaptor proteins ( Hynes, 2002 ). (biologists.org)
- Such signaling is important for the formation and turnover of cell-matrix adhesions, in which integrins and associated proteins are concentrated to mediate local, firm contact to the ECM. (biologists.org)
- downstream of integrins SFKs control guanine-exchange factors (GEFs) and GTPase-activating proteins (GAPs) that act on Rho-GTPases ( Fig. 1 ). (biologists.org)
- The central role played by receptor tyrosine kinases in the control of cell proliferation, differentiation, and metastasis of different types of cancers renders these proteins an attractive target for molecular-based cancer therapy. (aacrjournals.org)
- Heparin-mimicking sulfonic acid polymers as multitarget inhibitors of HIV-1 Tat and gp120 proteins" Antimicrobial Agents & Chemother. (unibs.it)
- Together with some previously well known deregulated proteins in CRC (β-catenin, c-MYC, or p63), we found new potential markers preferentially expressed in CRC tumors: cytokeratin 13, calcineurin, CHK1, clathrin light chain, MAPK3, phospho-PTK2/focal adhesion kinase (Ser-910), and MDM2. (mcponline.org)
- Only 10 proteins have been described that are effectively used as biomarkers ( e.g. prostate-specific antigen, carcinoembryonic antigen, and CA125) ( 1 ). (mcponline.org)
- Hence microarrays allow for a rapid identification of low expression proteins such as signaling molecules, cell cycle regulators, etc. (mcponline.org)
- The antibody microarray used in these studies contained 224 different antibodies ( 11 ), representing markers for eight biological pathways of interest (apoptosis, cell cycle, neurobiology, cytoskeleton, signal transduction, and nuclear proteins). (mcponline.org)
- Target proteins, the functions of which are modulated by Rho, include protein kinase N (PKN) ( 9 ), Rho-kinase ( 10 ) [also called Rho-binding kinase ( 11 )], and the myosin-binding subunit (MBS) of myosin phosphatase ( 12 ). (sciencemag.org)
- We produced four fragments containing these domains as glutathione-S-transferase (GST) fusion proteins: GST-CAT (catalytic domain, amino acids 6 to 553), GST-COIL (coiled-coil domain, amino acids 421 to 701), GST-RB (Rho-binding domain, amino acids 941 to 1075), and GST-PH (pleckstrin-homology domain, amino acids 1125 to 1388). (sciencemag.org)
- Furthermore, the negatively charged, sulfated GAGs of cell surface proteoglycans, but not their core proteins, were identified as the binding sites for DcR3.Fc. (ox.ac.uk)
- Structurally, the adapter proteins are characterized by containing multiple protein binding motifs. (asm.org)
- While many LIM proteins contain various other functional domains such as homeodomains or kinase domains, a subfamily of LIM proteins that are composed of only LIM domains (LIM-only proteins) has also been described. (asm.org)
- The small GTP-binding protein Rho is required for the formation of stress fibres and focal adhesions induced by growth factors such as lysophosphatidic acid (LPA) in serum-starved Swiss 3T3 cells, and for the LPA-induced tyrosine phosphorylation of several focal adhesion proteins. (ucl.ac.uk)
- Plating of cells on extracellular matrix proteins also stimulates protein tyrosine phosphorylation and the formation of stress fibres and focal adhesions in the absence of added growth factors. (ucl.ac.uk)
- Focal adhesion and stress fibre formation was also triggered by addition of a peptide GRGDS, which is recognised by a number of integrins and is contained within the cell binding domain of a variety of extracellular matrix proteins. (ucl.ac.uk)
- The Inhibitor of Apoptosis (IAP) proteins act downstream of a broad range of stimuli, such as cytokines and extracellular matrix interactions, to regulate cell survival, proliferation and migration. (omicsonline.org)
- The IAPs were first discovered in baculoviruses, where they were found to encode for proteins (cpIAP, OpIAP) able to inhibit apoptosis in the host cell [ 1 , 2 ]. (omicsonline.org)
- In addition, they phosphorylate scaffold proteins that have no enzymatic activity, such as linker for activation of T cells, SH2 domain-containing leukocyte protein of 76 kDa, and Cbl, which function as docking sites for Src homology 2 (SH2)/SH3-containing effector molecules ( 10 ). (jimmunol.org)
- Cell-cell adhesion molecules are integral membrane proteins that are associated with peripheral membrane proteins to regulate and integrate cell-cell adhesion-related phenomena. (molvis.org)
- Carboxy-terminal to this, they possess an unstructured domain containing multiple SH2 binding site motifs, which when tyrosine-phosphorylated allow interaction with SH2 domain containing proteins. (wikipedia.org)
-  For the better studied members of the CAS family ( BCAR1 and NEDD9 ), all of these domains have been defined as crucial for recognition and binding by other proteins, reflecting the primary role of CAS family proteins as cell signaling cascades mediators. (wikipedia.org)
- A meshwork of proteins called the extracellular matrix surrounds the cells that make up our tissues. (elifesciences.org)
- Integrins are adhesion proteins that sit on the membrane surrounding each cell and bind to the matrix proteins. (elifesciences.org)
- Previous research has shown that in certain types of blood cells, proteins called talins and kindlins perform this activation. (elifesciences.org)
- These proteins bind to the part of the integrin that extends into the cell, causing shape changes to the integrin that allow binding to the extracellular matrix. (elifesciences.org)
- Fibroblasts are cells that help to make extracellular matrix proteins, and are an important part of connective tissue. (elifesciences.org)
- The underlying mechanism involved activation of RhoA, a member of small GTP binding proteins, resulting in activation of focal adhesion kinase (FAK) and s1-integrin. (nii.ac.jp)
- We established a library of cancer cell lines that overexpress these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN . (nature.com)
- While anogenital HPV E6 proteins bind to a LXXLL motif on the ubiquitin ligase E6AP, BE6 binds to LXXLL motifs found on the cellular adapter protein paxillin, while HPV-16 E6 binds paxillin poorly ( 26 , 30 ). (asm.org)
- It localizes to focal adhesions and associates with focal adhesion proteins implicated in the regulation of cell attachment, spreading, and migration, including focal adhesion kinase (FAK), GIT1, PAK, Src, and Crk (reviewed in reference 6 and illustrated in Fig. 1 ). (asm.org)
- Paxillin tyrosine phosphorylation sites bind to the SH2-containing proteins Src (at Y31) and CRKL (at Y118). (asm.org)
- Paxillin regulates focal adhesion turnover, since cells from which paxillin has been deleted or that express paxillin mutants have delayed focal adhesion turnover and cell migration ( 33 , 34 ), and paxillin has been shown to influence the activity of proteins, including the Rho family of small GTP-binding proteins that are involved in regulating actin dynamics (reviewed in references 19 and 35 ). (asm.org)
- HIC-5 is a paxillin family member that is highly similar to paxillin but differs in its binding to FAK and GIT proteins and is differentially expressed in differentiated tissues and in response to morphogenic signaling ( 14 , 25 , 28 ). (asm.org)
- Yeast two-hybrid screening for angiostatin-binding proteins in a human placenta cDNA library. (nih.gov)
- Cells contain many proteins that are potentially involved in translating mechanical stimulation into biochemical signals that induce downstream processes. (royalsocietypublishing.org)
- One hallmark of focal adhesions is the clustering of integrins-membrane receptors with an extracellular domain that binds collagen and other ECM proteins and an intracellular domain that associates with the cytoskeleton through adapter proteins. (thermofisher.com)
- Integrin-mediated signaling requires the recruitment of many intracellular proteins to the focal adhesion, including focal adhesion kinase (FAK), a key regulator of adhesion and motility in normal and tumor cells. (thermofisher.com)
- Invitrogen offers a comprehensive portfolio of antibodies for studying the different phosphorylated FAK species, as well as the proteins that interact with them (Table 1). (thermofisher.com)
- Uncovering the mechanisms of FAK phosphorylation and dephosphorylation, as well as the interactions of FAK with other signaling proteins, is vital to the understanding of these cell processes. (thermofisher.com)
- Recent reports have shown that FAK colocalizes with the tight junction proteins occludin and ZO-1 , and that FAK contains nuclear localization signals consistent with a novel role in gene expression . (thermofisher.com)
- Focal adhesions are an elaborate network of interconnecting proteins linking actin stress fibers to the extracellular matrix substrate. (rupress.org)
- Vinculin does not bind directly to integrins, but does link actin filaments to integrin receptors through interactions with other focal adhesion proteins, such as talin ( Craig and Johnson 1996 ). (rupress.org)
- Although specific protein-protein interactions between many focal adhesions proteins have been identified, it is not clear how this multimeric complex of proteins organize to form a focal adhesion. (rupress.org)
- Ectodomain shedding of extracellular and membrane proteins is of fundamental importance for cell-cell communication in neoplasias. (clinsci.org)
- A Disintegrin And Metalloproteinase (ADAM) proteases constitute a family of multifunctional, membrane-bound proteins with traditional sheddase functions. (clinsci.org)
- Proteolytic degradation of extracellular matrix (ECM) components, cleavage of cell surface proteins, and subsequent release of soluble ectodomains promote cancer progression via induction of angiogenesis and metastasis. (clinsci.org)
- The leading edge or lamellipodium of migrating cells is the point at which integrins engage the extracellular matrix, an interaction that leads to integrin clustering into an array of small multiprotein focal complexes ( 31 ) containing an array of structural and signaling proteins that act to establish and maintain the polarity of the migrating cell. (asm.org)
- In addition to binding directly to integrin cytodomains, paxillin contains numerous protein-binding modules that interact with a variety of structural and signaling proteins and is therefore classified as a molecular adaptor or scaffold protein ( 23 ). (asm.org)
- LD domains are protein-protein interaction motifs with the consensus sequence LDXXLLXXL, and these mediate the interaction of paxillin with a number of proteins that regulate cell migration. (asm.org)
- LD1 binds integrin-linked kinase and the actin-binding proteins vinculin and actopaxin, while LD2 associates with focal adhesion kinase (FAK) and the ARF-GAP protein, p95PKL ( 23 ). (asm.org)
- Based on mutational analysis, Turner and coworkers ( 23 ) have identified the regions of proteins that associate with the various LD domains and termed them paxillin-binding subdomains or PBSs. (asm.org)
- Eukaryotic kinesin motor proteins utilize the energy of ATP hydrolysis to move cargoes, such as chromosomes and vesicles, along cytoskeletal microtubule networks . (cytoskeleton.com)
- Recent data show that GIT1 traffics between three distinct cellular compartments (cytoplasm, focal adhesions and cell membrane) through interactions with diverse proteins including ARF, Rac1 and Cdc42 GTPases, p21-activated kinase (PAK), PAK-interacting exchange factor (PIX) and paxillin. (ahajournals.org)
- When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (By similarity). (uniprot.org)
- In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). (uniprot.org)
- SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). (uniprot.org)
- The other main mechanism of entry described in Enterobacteriaceae is the trigger mechanism, which relies on the type III secretion system (T3SS) to inject effector proteins into the cytoplasm of the host cell where they activate various proteins belonging to the Rho family, including CDC42 and Rac1. (biomedcentral.com)
- When solid tumors including lymphomas metastasize and migrate from the original site of malignant change to faraway sites they could be especially challenging to take care of.3 Lymphocyte migration is along with a polarized redistribution of cytoskeletal proteins chemo-attractant receptors adhesion and signaling substances.4 5 Adhesion substances in such lymphocytes assemble into complexes at stage contacts set ups that act like the focal adhesions of fibroblasts. (exposed-skin-care.net)
- Pubmed ID: 12584338 Human herpesvirus 8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus, implicated in the pathogenesis of Kaposi's sarcoma, utilizes heparan sulfate-like molecules to bind the target cells via its envelope-associated glycoproteins gB and gpK8.1A. HHV-8-gB possesses the Arg-Gly-Asp (RGD) motif, the minimal peptide region of many proteins known to interact with subsets of host cell surface integrins. (jove.com)
- Subsequently, we demonstrated that ICAM-1 binding triggers calcium oscillations which may activate proteins involved in focal adhesion disassembly and cell contraction. (biomedcentral.com)
- 1999). The systems where PTH regulates FGF2 involve proteins kinase A (PKA)-cAMP and/or PKC pathway activation, since activators for PKA and PKC pathway all elevated FGF2 appearance, which mimicked the stimulatory aftereffect of PTH on FGF2 appearance (Hurley MM, 1999). (antibodyassay.com)
- Reflecting the increased amino acid transport capacity of tumor cells, F-18 fluroethyltyrosine (F-18 FET) is actively taken up in tumor cells via amino acid transport system L, but is neither incorporated into proteins nor readily degraded, resulting in high intracellular concentrations of this imaging agent. (cancer.gov)
- ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. (sdsc.edu)
- We find that Trop-2 does not modulate either protein or activation levels of the prominent FN receptors, β(1) integrins, but acts through increasing β(1) association with the adaptor molecule RACK1 and redistribution of RACK1 to the cell membrane. (nih.gov)
- Despite widespread expression, patients with TRPC6 mutations do not present with any other pathological phenotype suggesting that this protein has a unique but yet unidentified role within the target cell for FSGS, the kidney podocyte. (bristol.ac.uk)
- Vinculin, a paxillin-binding protein, was not altered by vascular injury or by eNOS gene transfer. (ahajournals.org)
- 1 2 3 4 5 At the focal adhesion sites, paxillin is associated with the actin filament-binding protein vinculin. (ahajournals.org)
- 4 5 6 Paxillin can directly associate with cytosolic protein tyrosine kinases, csk, crk, c-src, and focal adhesion kinase (FAK). (ahajournals.org)
- 6 10 SH2, together with SH3 and the LIM domains (a conserved sequence of Lin-11, IsI-1, and Mec-3) of paxillin, mediates protein-protein interactions. (ahajournals.org)
- 6 Tyrosine phosphorylation of paxillin is associated with cytokines, mitogenic peptides, growth factors, and extracellular matrix protein-stimulated signal transduction, including the mitogen-activated protein kinase pathway that is involved in cell migration and proliferation. (ahajournals.org)
- Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. (pnas.org)
- It was subsequently found to be a ubiquitous non-receptor protein tyrosine kinase ( 2 ), colocalizing with integrins at focal adhesions in adherent cells ( 3 - 5 ). (pnas.org)
- FAK is a non-receptor protein tyrosine kinase of 125 kD which directly interacts with β-subunit of integrin molecule, resides within the Focal Adhesion complex and initiates Integrin mediated signaling. (scirp.org)
- FAK is situated at the signaling junctions where information comes from mainly four sources-ECM-integrin interaction, growth factor signaling, G-protein coupled receptor signaling and mechanical forces imposed on the cell [1,2]. (scirp.org)
- Selectively, Yersinia enterocolitica strains producing the effector protein Yersinia outer protein P (YopP) hampered NF-κB activation and subsequently conferred apoptosis to J774A.1 macrophages. (jimmunol.org)
- A series of studies suggest that Yersinia blocks macrophage TNF-α production by down-regulation of mitogen-activated protein kinase (MAPK) activities ( 3 , 4 , 5 , 6 ). (jimmunol.org)
- Although the entire pathway has not yet been elucidated, previous work suggested that the signal events involved occurred primarily within the focal adhesion complex (where FAK and Src bind to the adapter protein paxillin), could be activated by the stimulation of pressure or shear acting on the cell, and could then modulate β 1 -integrin binding affinity. (aacrjournals.org)
- Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene. (wikipedia.org)
- The Cas family comprises other three members: NEDD9 (Neural precursor cell expressed, developmentally down-regulated 9, also called Human enhancer of filamentation 1, HEF-1 or Cas-L), EFS (Embryonal Fyn-associated substrate), and CASS4 (Cas scaffolding protein family member 4). (wikipedia.org)
- Given the ability of p130Cas/BCAR1 scaffold protein to convey and integrate different type of signals and subsequently to regulate key cellular functions such as adhesion, migration, invasion, proliferation and survival, the existence of a strong correlation between deregulated p130Cas/BCAR1 expression and cancer was inferred. (wikipedia.org)
- Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene. (wikipedia.org)
- This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. (wikipedia.org)
- The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration , nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. (wikipedia.org)
- This protein has been shown to bind a CRK-associated substrate, a nephrocystin, a GTPase regulator associated with FAK, and the SH2 domain of GRB2. (wikipedia.org)
- The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. (wikipedia.org)
- Focal adhesions can be considered to be large protein assembly complexes that spread mechanical forces from sites of cell adhesion to the cell body. (hindawi.com)
- Several protein kinases are recruited to focal adhesions upon cell attachment. (hindawi.com)
- FAK is a protein of M r 125 that localizes to focal adhesions ( 5 ) and is activated and tyrosine phosphorylated in response to integrin clustering ( 6 ). (aacrjournals.org)
- CureFAKtor's proprietary FAK technology platform may represent a significant breakthrough in the treatment of most solid tumor cancers in that its unique mechanism of action disrupts the signaling of specific protein to protein binding between FAK and tumors. (bio-medicine.org)
- Alpha-actinin is a cytoskeletal protein that binds to Vinculin and crosslinks Actin in actomyosin stress fibers and tethers them to focal contacts. (bio-rad.com)
- Zyxin is an Alpha-actinin and stress-fiber-binding protein found in mature contacts. (bio-rad.com)
- PIPKI gamma also can be stimulated by tyrosine-protein kinase c-Src [ 8 ] and FAK1 phosphorylation [ 9 ]. (bio-rad.com)
- Phosphorylation of FAK1 at Tyr925 mediated by c-Src creates a binding site for the Growth factor receptor-bound protein 2 ( GRB2 ), thereby leading to the activation of the Extracellular signal-regulated kinase-1/2 ( ERK1/2 ). (bio-rad.com)
- Conserved domains in ADAM family members include a prodomain, a zinc-dependent metalloprotease domain, a disintegrin domain, a cysteine-rich domain, an EGF-like sequence, and a short cytoplasmic tail (1,2).The prodomain is thought to aid in protein folding. (cellsignal.com)
- All SignalSilence® siRNA products from CST are rigorously tested in-house and have been shown to reduce protein expression in specified cell lines. (cellsignal.com)
- Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). (cellsignal.com)
- The intercellular space in cell-cell junctions is maintained at 20 nm Adhesive junctions Adherens junctions (or zonula adherens, intermediate junction, or 'belt desmosome') are protein complexes that occur at cell-cell junctions in epithelial tissues, usually more basal than tight junctions. (prezi.com)
- It is implicated in cell-motility responses upon activation of cell-surface receptors and can recruit, among others, the GIT1 [GRK (G-protein-coupled-receptor kinase)-interacting ARF (ADP-ribosylation factor) GAP (GTPase-activating protein)]-PIX [PAK (p21-activated kinase)-interacting exchange factor]-PAK1 complex. (biochemj.org)
- Selective inhibition of a known target of staurosporine, protein kinase C, using GF109203X, and of phosphoinositide 3′-kinase using wortmannin, did not reduce FAK tyrosine phosphorylation at Tyr 861 and Tyr 397 , or cause disruption of focal adhesions. (portlandpress.com)
- Cycloheximide, the protein synthesis inhibitor, induced PAEC apoptosis more slowly than staurosporine, but did not induce FAK dephosphorylation or rapid focal adhesion disruption, and instead caused a slower loss of focal adhesions and a marked increase in FAK proteolysis. (portlandpress.com)
- 1 The receptor for u-PA (u-PAR) is a 55-65 kDa glycosylphosphatidylinositol-linked protein that binds the epidermal growth factor-(EGF)-like domain (amino acids 20-32) of two chain u-PA. (bmj.com)
- Cell-matrix adhesions function not only as structural anchor points that organize the actin cytoskeleton, but are also coupled to components of the actin-assembly machinery, such as actin-related protein 2/3 (Arp2/3). (biologists.org)
- Dependent on their cellular localization, Protein Kinase D (PKD) enzymes regulate different processes including Golgi transport, cell signaling and response to oxidative stress. (elsevier.com)
- The localization of PKD within cells is mediated by interaction with different lipid or protein binding partners. (elsevier.com)
- We previously reported that the adhesion G-protein-coupled receptor GPR56/ADGRG1 is downregulated in melanoma metastases. (frontiersin.org)
- We have recently shown that macrophage-stimulating protein (MSP) promotes the invasion of recepteur d'origine nantais (RON), a tyrosine kinase receptor-positive MDA-MB-231, MDA-MB-468 breast cancer cells, and also identified the regulatory elements required for RON gene expression. (aacrjournals.org)
- Reverse transcription-PCR and Western analysis indicated the down-regulation of the RON message and protein, respectively, in MDA-MB-231 and MDA-MB-468 cells. (aacrjournals.org)
- The RON receptor activates an array of downstream signaling cascades such as phosphoinositide-3-kinase/Akt, focal adhesion kinase, and mitogen-activated protein kinases which are involved in cell proliferation, tubular morphogenesis, cell motility, migration, and invasion ( 6 - 9 ). (aacrjournals.org)
- Previously we found that CIB1, a 22 kDa regulatory protein, plays a critical role in endothelial cell function, angiogenic growth factor-mediated cellular functions, PAK1 activation, MMP-2 expression, and in vivo ischemia-induced angiogenesis. (pubmedcentralcanada.ca)
- CIB1 is a 22 kDa EF-hand-containing regulatory protein that was originally identified as a binding partner for the cytoplasmic tail of the platelet integrin αIIb, and later found to inhibit αIIbβ3 activation in megakaryocytes [ 8 , 9 ]. (pubmedcentralcanada.ca)
- The NLS of the HIV-1 Tat protein interacts with the fd bacteriophage and with a peptide derived from its p8 protein" Antiviral Res. (unibs.it)
- Other targets of Rho with unknown functions include rhophilin, p160 Rho-associated coiled-coil-containing protein kinase (ROCK), rhotekin, citron ( 9 , 14 ), and phosphatidylinositol-4-phosphate 5-kinase (PIP5-K) ( 15 ). (sciencemag.org)
- Serine-threonine kinases such as protein kinase C (PKC) and Raf are usually composed of regulatory and catalytic domains ( 16 ). (sciencemag.org)
- Here we show that tumstatin functions as an endothelial cell-specific inhibitor of protein synthesis. (sciencemag.org)
- Through a requisite interaction with αVβ3 integrin, tumstatin inhibits activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3-kinase), protein kinase B (PKB/Akt), and mammalian target of rapamycin (mTOR), and it prevents the dissociation of eukaryotic initiation factor 4E protein (eIF4E) from 4E-binding protein 1. (sciencemag.org)
- These results establish a role for integrins in mediating cell-specific inhibition of cap-dependent protein synthesis and suggest a potential mechanism for tumstatin's selective effects on endothelial cells. (sciencemag.org)
- Apoptosis, or programmed cell death, is regulated in part at the level of protein synthesis ( 1-4 ). (sciencemag.org)
- Because apoptosis is generally associated with inhibition of cap-dependent translation, we investigated the effect of tumstatin on protein synthesis in endothelial cells ( 9 ). (sciencemag.org)
- At maximal dose (22.7 μM), tumstatin peptide T3 was found to inhibit protein synthesis in cultured bovine endothelial cells by 45% ( Fig. 1 A). At molar equivalent concentrations (4.5 μM), all tumstatin peptides inhibited protein synthesis by 25 to 30% ( Fig. 1 , B and C) ( 11 ). (sciencemag.org)
- Tumstatin peptides inhibit total protein synthesis and cap-dependent protein translation in endothelial cells. (sciencemag.org)
- Our findings suggest that early activation of p42/44 ERK MAPK (5 min), early growth response-1 (Egr-1), and activator protein-1 (AP-1) DNA-binding activity (30 min) as well as subsequent hepatocyte proliferation (24-72 hr) in response to 70% PH were impaired in P2Y2-/- mice. (jove.com)
- Extracellular ATP alone, via activation of P2Y2 purinergic receptors, was sufficient to induce ERK phosphorylation, Egr-1 protein expression, and key cyclins and cell cycle progression of hepatocytes in vitro. (jove.com)
- Moreover, a fusion protein comprising the GAG-binding region of DcR3 with an Fc fragment (DcR3_HBD.Fc) has the same effect as DcR3.Fc in activating protein kinase C and inducing cell adhesion. (ox.ac.uk)
- We report here that PINCH is a binding protein for integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase that plays important roles in the cell adhesion, growth factor, and Wnt signaling pathways. (asm.org)
- Additionally, biochemical studies indicate that ILK, through the interaction with PINCH, is capable of forming a ternary complex with Nck-2, an SH2/SH3-containing adapter protein implicated in growth factor receptor kinase and small GTPase signaling pathways. (asm.org)
- These results demonstrate a specific protein recognition mechanism utilizing a specific LIM domain and multiple ANK repeats and suggest that PINCH functions as an adapter protein connecting ILK and the integrins with components of growth factor receptor kinase and small GTPase signaling pathways. (asm.org)
- Many of the essential cellular processes, including cell proliferation, differentiation, and survival, are controlled by signal transduction pathways involving specific protein-protein interactions. (asm.org)
- The LIM domain is a protein binding motif consisting of a cysteine-rich consensus sequence of approximately 50 amino acids that fold into a specific three-dimensional structure comprising two zinc fingers ( 6 , 11 ). (asm.org)
- Recently, we have found that PINCH interacts with Nck-2, an SH2/SH3-containing adapter protein physically associated with key components of small GTPase- and growth factor receptor kinase signaling pathways, including IRS-1 and receptors for epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) ( 26 ). (asm.org)
- The cagA -encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase, a bona fide oncoprotein in human malignancies. (pnas.org)
- The cagA -encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system ( 8 ), where it undergoes tyrosine phosphorylation by Src or Abl kinase at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs present in variable numbers in the C-terminal region ( 9 - 12 ). (pnas.org)
- Objective- The G-protein-coupled receptor kinase interacting protein-1 (GIT1) is a scaffold protein that is important for phospholipase Cγ and extracellular signal-regulated kinase 1/2 signaling induced by angiotensin II and epidermal growth factor. (ahajournals.org)
- Among these signals, we found that a key molecule was the GPCR-kinase interacting protein-1 (GIT1). (ahajournals.org)
- Moreover, mutagenesis data indicate that the bacterial fibronectin-binding protein CadF and the intact flagellum are involved in Rho GTPase activation and host cell invasion. (frontiersin.org)
- Zyxin is one protein implicated in regulating cellular responses to mechanical and stress forces applied to sites of adhesion. (biologists.org)
- If you require a native form of the protein please use the live cell version - found here . (abcam.com)
- Belongs to the protein kinase superfamily. (abcam.com)
- STE Ser/Thr protein kinase family. (abcam.com)
- Contains 1 protein kinase domain. (abcam.com)
- Insulin-like growth factor II receptor as a multifunctional binding protein. (springer.com)
- also known as PTK2 protein tyrosine kinase 2) is important in cell migration, as its signaling pathways are key to the formation of focal adhesions that aid in the adhering of cells to the extracellular matrix. (biolegend.com)
- The activation of protein C requires thrombin binding to the EGF-like domain and is enhanced by a second site binding to the chondroitin sulfate (CS) moiety attached to the serine/threonine-rich domain [ 12 ]. (biomedcentral.com)
- The Zap70 protein tyrosine kinase controls TCR-linked signal transduction pathways and is critical for T cell development and responsiveness. (jimmunol.org)
- We have shown previously that the CT10 regulator of kinase II (CrkII) adapter protein interacts with tyrosine-phosphorylated Zap70 in TCR-engaged T cells, and now extend these studies to show that Tyr 315 in the Zap70 interdomain B region is the site of interaction with CrkII. (jimmunol.org)
- Phosphorylation of Tyr 315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. (jimmunol.org)
- Whereas the TCR subunits are devoid of enzymatic activity, several nonreceptor protein tyrosine kinases (PTKs), 3 which are constitutively associated with, or recruited to the activated TCR, mediate the phosphorylation of the receptor subunits, as well as other substrates at the immunological synapse. (jimmunol.org)
- More specifically, my research interest lies in identifying protein targets or cell populations responsible for chronic illnesses such as Triple Negative Breast Cancer and Alzheimer?s disease. (stanford.edu)
- Retinas of newborn, juvenile, and adult Callithrix jacchus and Macaca fascicularis monkeys and control human retinas were studied to determine the localization of angiostatin relative to III β-tubulin, glial fibrillary acidic protein, vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM), and the angiostatin receptor αvβ3-integrin in the foveal, macular, and peripheral retina. (arvojournals.org)
- A key component of junctional complexes that regulates TJs formation is zonula occludens-1 (ZO-1), which is a 210-225 kDa protein of the membrane-associated guanylate kinase homologs gene family [ 14 , 15 ] and is shown to be indispensible for TJ formation. (molvis.org)
- engineered mouse fibroblast cells to lack either talin or kindlin, and found that both of these mutant cell types were unable to activate their integrins and as a result failed to bind to an extracellular matrix protein called fibronectin. (elifesciences.org)
- found that this cell shape is dependent on kindlin and its ability to bind to and recruit a protein called paxillin to "adhesion sites", where integrins connect the cell surface with the extracellular matrix. (elifesciences.org)
- Focal adhesion kinase (FAK) is a non-receptor protein-tyrosine kinase implicated in signaling pathways involved in cell motility, proliferation and apoptosis (1). (novusbio.com)
- FAK is activated by phosphorylation at tyrosine 397 in response to integrin clustering which can be induced by cell adhesion or antibody cross-linking or via G-protein-coupled receptor (GPCR) occupancy by ligands such as bombesin or lysophosphatidic acid (2-3). (novusbio.com)
- The bovine papillomavirus type 1 E6 (BE6) binds to LXXLL peptide sequences termed LD motifs (consensus sequence LDXLLXXL) on the cellular protein paxillin that is a substrate of Src and focal adhesion kinases. (asm.org)
- Paxillin was first identified as a hyperphosphorylated protein in Src transformed cells. (asm.org)
- Glutathione S -transferase (GST) and maltose-binding protein (MBP) fusions to BE6 and paxillin and paxillin mutants have been previously described ( 30 ). (asm.org)
- Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. (nih.gov)
- Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells.Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility.These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells. (nih.gov)
- Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. (nih.gov)
- Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. (nih.gov)
- We generated a Gal4-binding domain fusion protein containing the kringle domains 1-4 of angiostatin. (nih.gov)
- Focal adhesions allow diverse protein activities to concentrate at the cell membrane, providing both an anchorage for attachment to surrounding tissues and a conduit for transduction of signals between the cell and its environment. (thermofisher.com)
- FAK, a nonreceptor protein tyrosine kinase, is expressed in most tissues and cell types and is highly conserved across mammalian and other eukaryotic species . (thermofisher.com)
- The FAK protein contains four distinct domains: the catalytic kinase core lies between the N-terminal FERM (band 4.1, ezrin, radixin, moesin) domain and the C-terminal FAT (focal adhesion targeting) domain, and an unstructured proline-rich area is found between the catalytic and FAT domains [1-4]. (thermofisher.com)
- These effects depend on ET A R activation and involve multiple mitogen-activated protein kinase (MAPK) signaling pathways, including p42/44 MAPK, p38 MAPK, and transactivation of the epidermal growth factor receptor. (aacrjournals.org)
- Strong evidence implicates the small GTP-binding protein Rho in the formation of focal adhesions and stress fibers ( Hall 1998 ). (rupress.org)
- We and others have shown that activation of the Raf-1/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2)/ERK1/2 signaling cascade is associated with alteration in cellular morphology and neuroendocrine phenotype ( 4 - 6 ), suggesting that this signaling cascade may regulate the metastatic and neuroendocrine phenotypes of BON carcinoid tumor cells. (aacrjournals.org)
- Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase that localizes to focal adhesions, sites of integrin engagement with the extracellular matrix ( 7 ). (aacrjournals.org)
- The focal adhesion targeting sequence contains a binding site for tyrosine-phosphorylated adaptor protein that recruits multiple signaling molecules into complex via a Src homology (SH2) domain mediated interaction ( 8 ). (aacrjournals.org)
- In many cell types, FAK activation leads to the SH2 domain-mediated binding of Src family protein-tyrosine kinases to the motif surrounding the FAK Tyr397 phosphorylation site ( 9 ). (aacrjournals.org)
- Src also phosphorylates FAK at Tyr 407 , Tyr 861 , or Tyr 925 , creating docking sites for other SH2 domain-bearing molecules, such as growth factor receptor binding protein 2, which links FAK to activation of the MAPK cascade ( 7 , 10 , 11 ). (aacrjournals.org)
- The cytoplasmic domain is critical for that activation and involves focal adhesion kinase (FAK), extracellular regulated kinase (ERK1/2), and protein kinase B (AKT/PKB) signaling, further contributing to cancer progression and mediating chemoresistance against first-line therapies. (clinsci.org)
- The NDRG1 (N- myc downregulated gene-1) gene encodes a growth-related protein, and its transcription can be induced in response to stress. (physiology.org)
- Depletion of cellular polyamines by inhibiting ornithine decarboxylase (ODC) with α-difluoromethylornithine not only induced p53 but also increased NDRG1 transcription as indicated by induction of the NDRG1 promoter activity and increased levels of NDRG1 mRNA and protein, all of which were prevented by using specific p53 siRNA and in cells with a targeted deletion of p53. (physiology.org)
- In addition to uPAR, cytokeratin 8 (CK8) is an important plasminogen-binding protein in the membrane of breast cancer cells. (biomedcentral.com)
- CK8 is an intermediate filament protein and associates with CK18 to form an insoluble matrix within the cell. (biomedcentral.com)
- These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment. (rcsb.org)
- We have previously identified poly(A)-binding protein 1 (PABP1) as a ligand for paxillin and shown that the paxillin-PABP1 complex undergoes nucleocytoplasmic shuttling. (asm.org)
- The 68-kDa protein paxillin is an abundant component of focal complexes at the leading edge of migrating cells. (asm.org)
- Using a proteomic approach, we have recently identified an association between paxillin and the mRNA-binding protein, PABP1. (asm.org)
- We previously showed that the G-protein coupled receptor (GPCR) kinase-interacting protein 1 (GIT1) was a key mediator for thrombin-mediated endothelial cell (EC) focal adhesion turnover and permeability. (ahajournals.org)
- ZmBSK1 localizes in plasma membrane, interacts with calcium/calmodulin (Ca2+ /CaM)-dependent protein kinase (ZmCCaMK), and phosphorylates ZmCCaMK. (bvsalud.org)
- Calcium (Ca2+)/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of abscisic acid (ABA) and abiotic stress signaling in plants and is believed to act upstream of mitogen-activated protein kinase (MAPK) in ABA signaling. (bvsalud.org)
- Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. (uniprot.org)
- SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. (uniprot.org)
- The Src protein was highly expressed in tumor cells, but expression did not correlate with survival. (aacrjournals.org)
- Receptor insulinu sličnog faktora rasta 1 je protein koji je prisutan na površini ljudskih ćelija . (wikipedia.org)
- The protein tyrosine kinase v-Src is the transforming product of Rous sarcoma virus, the first identified oncogenic retrovirus. (biologists.org)
- The monoclonal antibody portion of the F16-IL2 fusion protein binds to tumor cells expressing the tumor associated antigen (TAA) tenascin-C. In turn, the IL-2 moiety of the fusion protein stimulates natural killer (NK) cells, macrophages and neutrophils and induces T-cell antitumor cellular immune responses thereby selectively killing tenascin-C-expressing tumor cells. (cancer.gov)
- Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1 , ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. (sdsc.edu)
- These enhanced Src and FAK activities are not mediated by changes in either the activity of IGF-IR, which is known to bind RACK1, or IGF-IR's ability to associate with β(1) integrins. (nih.gov)
- Integrins are the receptors through which cells attach with ECM. (scirp.org)
- Among the regulators of p130Cas/BCAR1 tyrosine phosphorylation, receptor tyrosine kinases (RTKs) and integrins play a prominent role. (wikipedia.org)
- Integrins are heterodimeric cell surface adhesion receptors formed by two noncovalently associated subunits, alpha and beta. (bio-rad.com)
- The ECM, integrins and the cell cytoskeleton interact at sites called focal contacts [ 4 ]. (bio-rad.com)
- Disintegrin and cysteine-rich domains mediate adhesion, at least in part, through binding to integrins. (cellsignal.com)
- The survival of endothelial cells is dependent on interactions between the matrix and integrins mediated through focal adhesions. (portlandpress.com)
- Keywords: integrin adhesion cytoskeletal stress cell extender micropost array cell dispersing 1 Launch The binding of integrins to extracellular matrix (ECM) initiates cell adhesion which may be described as some procedures including cell dispersing against the root matrix set up of focal adhesions (FAs) and era of actomyosin-mediated cytoskeletal stress against these adhesions . (exposed-skin-care.net)
- We assessed these pushes by culturing cells on FN-functionalized arrays of uniformly spaced elastomeric microposts something we created previously to allow studies of extender dynamics [5 14 Our data suggest which the activation condition of integrins is definitely intimately connected to fundamental adherent cell behaviours like contractility which has implications for improving our understanding of the rules of cell shape mechanics and function. (exposed-skin-care.net)
- 16 Although u-PAR lacks a transmembrane and intracellular domain and, therefore, intrinsic signal transduction potential, its ability to associate with cytoskeletal components and/or integrins at sites of focal contact 3 8 17-20 is a likely explanation for this phenomenon. (bmj.com)
- For example, u-PAR regulates cellular adhesion and migration by modifying the adhesive properties of integrins, 20 and by binding to the extracellular matrix component, vitronectin. (bmj.com)
- Binding of integrins to ECM triggers phosphorylation of two major components of FAs, focal adhesion kinase (FAK) and Src, activating downstream signaling pathway which leads to FA disassembly and cell migration. (hindawi.com)
- FAs transduce signals from the extracellular matrix into the cell via integrins clustering and subsequent activation of signaling pathways. (hindawi.com)
- Over the past years, it has become clear that there is extensive crosstalk between integrins, Src-family kinases and Rho-family GTPases at the heart of such adhesion signaling. (biologists.org)
- Cells interact with ECM components through various receptors, including integrins. (biologists.org)
- Actin stress fibers are linked to integrins at the inner surface of the plasma membrane through focal adhesions ( 1 , 2 ). (sciencemag.org)
- Finally, we have found that PINCH is concentrated in peripheral ruffles of cells spreading on fibronectin and have detected clusters of PINCH that are colocalized with the α5β1 integrins. (asm.org)
- The activity of the GRGDS peptide was blocked by microinjecting cells with C3 transferase, suggesting that peptide binding to integrins stimulates a Rho-dependent assembly of focal adhesions. (ucl.ac.uk)
- Integrins require an activation step prior to ligand binding and signaling. (elifesciences.org)
- Our findings show that talin and kindlin cooperatively activate integrins leading to FN binding and adhesion, and that kindlin subsequently assembles an essential signaling node at newly formed adhesion sites in a talin-independent manner. (elifesciences.org)
- Before integrins can bind to the extracellular matrix they must be activated. (elifesciences.org)
- However, it is not clear whether talin and kindlin also activate integrins in other cell types. (elifesciences.org)
- Even when cells were artificially induced to activate integrins by treating them with manganese ions, cells lacking talin or kindlin failed to fully activate integrins and hence did not adhere well to fibronectin. (elifesciences.org)
- The next challenge is to understand how talin and kindlin are activated in non-blood cells and how they maintain integrins in an active state. (elifesciences.org)
- Integrins are heterodimeric transmembrane receptors that mediate cell adhesion to the extracellular matrix (ECM) and to other cells ( Hynes, 2002 ). (elifesciences.org)
- The quality and strength of integrin signaling is controlled by the interaction between integrins and substrate-attached ligands, which is, in turn, regulated by the on- and off-rates of the integrin-ligand binding process. (elifesciences.org)
- The on-rate of the integrin-ligand binding reaction (also called integrin activation or inside-out signaling) is characterized by switching the unbound form of integrins from an inactive (low affinity) to an active (high affinity) conformation. (elifesciences.org)
- The formation of focal adhesions is initiated by the binding of integrins to specific extracellular matrix ligands and subsequent clustering of these receptors ( Burridge and Chrzanowska-Wodnicka 1996 ). (rupress.org)
- Integrins are the major family of cell surface receptors that mediate cell attachment to the ECM and can also mediate cell-cell interactions (Hynes, 1992 , 1999 ). (wiley.com)
- The β 1 integrins are the most prominent integrin subfamily, and the β 1 subunit can interact with 12 different α subunits to form functional receptors. (wiley.com)
- 1996 ). β 1 integrins have been implicated in mediating neurite outgrowth, cell migration, and proliferation during retinal morphogenesis (Cohen et al. (wiley.com)
- With the disintegrin (DIS) domain ADAM8 binds integrins such as β1 integrin, thereby activating integrin signaling pathways. (clinsci.org)
- On the other hand, the cytoskeleton itself can undergo rearrangements as a result of outside-in signals triggered by fibronectin binding to cell surface receptors, the integrins. (biomedcentral.com)
- Arrest of cell migration is usually associated with rearrangements of the actin cytoskeleton and activation of integrins that lead to the formation of large and stable focal adhesions. (exposed-skin-care.net)
- Background: The Ret proto-oncogene (c-Ret) is a receptor tyrosine kinase that functions as a multicomponent receptor complex in conjunction with other membrane-bound, ligand-binding GDNF family receptors (1). (cellsignal.com)
- Eph receptors and ephrins have been shown to affect the growth, migration and invasion of cancer cells in culture as well as tumour growth, invasiveness, angiogenesis and metastasis in vivo. (nih.gov)
- Phosphotyrosine phosphatases bind Eph receptors and ephrins to dampen or terminate their activity through dephosphorylation. (nih.gov)
- Integrin receptors go through conformational activation from a minimal affinity to high affinity condition [8 9 and these adjustments in integrin activity BMS-265246 may donate to the legislation of cell dispersing and FA set up. (exposed-skin-care.net)
- Moreover, overexpression of both IGF-IR and IR-A in breast cancer cells, leads to overexpression of hybrid IR/IGF-IR receptors (HRs) as well. (springer.com)
- These plaquelike structures link bundles of actin microfilaments, or stress fibers, to the extracellular matrix via transmembrane integrin and syndecan receptors, resulting in firm adherence of the cell to the substrate. (rupress.org)
- The process is accelerated if plasminogen and plasminogen activator are bound to their cell surface receptors. (biomedcentral.com)
- It integrates signals generated by stimulated surface membrane receptors, such as insulin receptor and integrin beta 1 receptor, and modulates their signal transduction in appropriate reaction sequences. (biomedcentral.com)
- Importantly, we and others showed that tyrosine kinase receptors (TKRs) such as the epidermal growth factor receptor stimulate GIT1 phosphorylation via c-Src, suggesting a role for GIT1 in TKR signaling. (ahajournals.org)
- In these species, adhesin molecules on the surface of the bacteria interact with receptors on the surface of the host cell. (biomedcentral.com)
- Under experimental SNX-2112 conditions activation of T-cell receptors or exposure to phorbol esters pharmacological analogs of the endogenous PKC activator Diacyl Glycerol (DAG) lead to LFA-1 activation. (exposed-skin-care.net)
- It's been suggested that during LFA-1 clustering several signaling substances touch one another thus producing a transformation of integrin conformation.14 Individual LFA-1 receptors possess three discrete conformational expresses seen as a low. (exposed-skin-care.net)
- HHV-8 utilizes alpha3beta1 integrin as one of the receptors for its entry into the target cells via its gB interaction and induces the activation of focal adhesion kinase (FAK) (S. M. Akula, N. P. Pramod, F.-Z. Wang, and B. Chandran, Cell 108:407-419, 2002). (jove.com)
- Abstract -Injury-caused dedifferentiation accompanied by proliferation and migration of smooth muscle cells (SMCs) is an important process in the development of the neointima. (ahajournals.org)
- Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory function. (pnas.org)
- Compared with control cells expressing wild-type FAK, FAK-null cells showed a decrease in migration speed and directional persistence. (pnas.org)
- Cells expressing Y397F FAK, which cannot be phosphorylated at a key tyrosine site, showed similar defects in migration pattern and force-induced reorientation as did FAK-null cells. (pnas.org)
- In addition, phosphorylation at Tyr-397 is required for some, but not all, of the functions of FAK in cell migration. (pnas.org)
- There is evidence that FAK is essential for integrin-stimulated cell migration ( 11 - 17 ), cell spreading ( 16 ), and proliferation ( 11 , 18 , 19 ). (pnas.org)
- Overexpression of FAK increases the migration rate ( 20 ), whereas abolition of FAK expression impairs cell migration and leads to embryonic lethality ( 21 ). (pnas.org)
- Tyr-397 autophosphorylation site is required for the maximal adhesion-induced FAK activation and for FAK-enhanced cell spreading and migration ( 16 ). (pnas.org)
- However, because the turnover of focal adhesion is closely coupled to cell migration, it is possible that the increase in size or stability of the focal adhesion is associated with other defects in cell migration. (pnas.org)
- There is increasing evidence that mechanical signals regulate not only cell migration, but also cell growth, apoptosis, and gene expression ( 22 - 26 ). (pnas.org)
- Experiments with flexible substrates demonstrated that both mechanical forces and substrate rigidity could profoundly affect cell shape and migration rate ( 27 ). (pnas.org)
- FAK was found to be involved in regulation of breast cancer cell migration and MMP-9 expression, activity. (scirp.org)
- Moreover, FAK signal was found to be transduced through ERK and PI3K, which modulate MMP-9 and thereby cell migration. (scirp.org)
- FAK regulates MMP-9 expression and activity and thereby migration of human breast cancer cell. (scirp.org)
- By the regulation of FAK, cell attachment and migration may be regulated by Curcumin, ATRA or EGCG treatment. (scirp.org)
- One of the common crucial events for cell migration, survival, apoptosis or cell proliferation is cell attachment with Extra Cellular Matrix (ECM). (scirp.org)
- These studies propose cell adhesion to FN may induce MMP-9 expression which finally facilitate cellular activities like migration, invasion. (scirp.org)
- This study is the first to analyse the soluble factors secreted by the bronchial epithelium after exposure to isophorone diisocyanate (IPDI) that are responsible for increasing migration and proliferation of primary normal human bronchial smooth muscle cells (BSMCs). (biomedsearch.com)
- Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased focal adhesion kinase (FAK), Src, extracellular signal-regulated kinase (ERK)1/2 and AKT activation. (biomedsearch.com)
- Due to its ability to associate with multiple signaling partners, p130Cas/BCAR1 contributes to the regulation to a variety of signaling pathways leading to cell adhesion, migration, invasion, apoptosis, hypoxia and mechanical forces. (wikipedia.org)
- RTK-dependent p130Cas/BCAR1 tyrosine phosphorylation and the subsequent binding with specific downstream signaling molecule modulate cell processes such as actin cytoskeleton remodeling, cell adhesion, proliferation, migration, invasion and survival. (wikipedia.org)
- Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. (hindawi.com)
- The ECM provides the scaffold for cell attachment which is necessary for several diverse cellular activities, including cytoskeletal remodeling, polarization, differentiation, migration, and invasion [ 7 - 9 ]. (hindawi.com)
- FAK is a 125 kDa cytoplasmic tyrosine kinase that is activated upon integrin engagement and controls signaling pathways crucial for cell proliferation, migration, and survival [ 37 ]. (hindawi.com)
- Cell migration is a coordinated process that involves rapid changes in the dynamics of actin filaments, together with the formation and disassembly of cell adhesion sites. (bio-rad.com)
- BACKGROUND Migration of colonic epithelial cells is important for mucosal repair following injury. (bmj.com)
- The urokinase (u-PA) system regulates migration in other cell types. (bmj.com)
- AIM To examine the role of u-PA and its receptor (u-PAR) in colonic epithelial cell migration. (bmj.com)
- METHODS Migration was assessed over 24 hours in circular wounds made in confluent monolayers of LIM1215 and Caco-2 human colon cancer cells. (bmj.com)
- RESULTS Migration was stimulated two to threefold by exogenous u-PA, an effect dependent on u-PAR binding but independent of u-PA mediated mitogenesis and proteolysis. (bmj.com)
- Basal migration and the motogenic effects of butyrate, epidermal growth factor, and phorbol-12-myristate-13-acetate were suppressed by the u-PAR antisense oligonucleotide (40-60%) but were at best minimally affected following inhibition of u-PA expression and binding. (bmj.com)
- CONCLUSIONS In an in vitro model of wounded colonic epithelium, u-PAR promotes cell migration through mechanisms that are not exclusively dependent on u-PA binding. (bmj.com)
- 3 4 The catalytic activity of u-PA is known to regulate the metastasis of cancer cells (reviewed by Andreason and colleagues 5 ) and migration of normal corneal epithelial cells over their native matrix in vitro. (bmj.com)
- Migration of a range of cell types over an artificial substratum in vitro is dependent on the binding of u-PA but not on its proteolytic activity. (bmj.com)
- Cell adhesion and migration are key determinants in tumor metastasis. (hindawi.com)
- During the process of tumor metastasis and more generally cell migration, cells connect with the microenvironment in part through focal adhesions (FAs) [ 1 ]. (hindawi.com)
- This in turn regulates cell migration by controlling the focal complex assembly/disassembly cycle at the leading lamellipodia of migrating cells, while also controlling adhesion disassembly at the trailing edge. (hindawi.com)
- Several other studies have shown that phosphorylation of FAK is associated with FA disassembly and thus regulates cell migration [ 9 - 12 ]. (hindawi.com)
- We also discuss how this signaling network can regulate a range of cellular processes that are important for normal tissue function and disease, including cell adhesion, spreading, migration and mechanotransduction. (biologists.org)
- The presence and regulation of PKD2 at focal adhesions identifies a novel function for this kinase as a modulator of cell adhesion and migration. (elsevier.com)
- An increase was also observed in the migration of epithelial cells along the villus, as revealed by [3H]thymidine incorporation and autoradiography in rats fed 900 ppm Sn2+ for 4 weeks. (tudelft.nl)
- A number of cell types must enter the wound in a relatively coordinated fashion, and this is controlled, in part, by modulating both the increased random and directed migration of cells. (springer.com)
- In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. (nih.gov)
- The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals. (nih.gov)
- Treatment of rat aortic smooth muscle cells with GIT1 small interfering RNA impaired cell migration. (ahajournals.org)
- Both phospholipase Cγ and extracellular signal-regulated kinase 1/2 signaling were required for GIT1-dependent VSMC proliferation and migration, whereas only phospholipase Cγ was involved in GIT1-mediated VSMC apoptosis. (ahajournals.org)
- Conclusions- GIT1 is a novel mediator of vascular remodeling by regulating VSMC proliferation, migration, and apoptosis through phospholipase Cγ and extracellular signal-regulated kinase 1/2 signaling pathways. (ahajournals.org)
- The proliferation and migration of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis and restenosis after angioplasty. (ahajournals.org)
- 10 In addition, our laboratory showed that GIT1 is required for ERK1/2 translocation and activation in focal adhesions, which are important for cell spreading and migration. (ahajournals.org)
- 9 , 11 Based on these data, we propose that GIT1 is essential for VSMC proliferation, apoptosis, and migration through PLCγ and ERK1/2 pathway induced by GPCR and tyrosine kinase receptor, which subsequently affects vascular remodeling. (ahajournals.org)
- Expression of TM enhanced cell migration and adhesion/spreading onto type I collagen, but had no effect on cell proliferation. (biomedcentral.com)
- Knocking down TM with short hairpin RNA reduced PDGF-stimulated adhesion and migration of human aortic VSMCs. (biomedcentral.com)
- Furthermore, the TM mutant (TM S490, 492A ) devoid of CS moiety failed to increase cell adhesion, spreading or migration. (biomedcentral.com)
- Wild-type TM, but not TM S490, 492A , increased focal adhesion kinase (FAK) activation during cell adhesion, and TM-enhanced cell migration was abolished by a function-blocking anti-integrin β 1 antibody. (biomedcentral.com)
- Chondroitin sulfate modification is required for TM-mediated activation of β 1 -integrin and FAK, thereby enhancing adhesion and migration activity of VSMCs. (biomedcentral.com)
- Migration and proliferation of vascular smooth muscle cells (VSMCs) are key events in the intimal thickening of atherosclerosis and neointimal formation induced by vascular injury [ 1 ]. (biomedcentral.com)
- Recent evidence further showed that the forced expression of TM in TM-deficient A2058 melanoma cells enhances cell adhesion, migration, and invasion through the activation of focal adhesion kinase (FAK) [ 10 ]. (biomedcentral.com)
- 2 - 5 Retinal ganglion cells (RGCs) express VEGF strongly during retinal development and inhibit the migration of astrocytes and endothelial cells into the macula. (arvojournals.org)
- In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. (nih.gov)
- Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. (nih.gov)
- However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. (nih.gov)
- These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells. (nih.gov)
- This last class of cellular cues, mechanical signals, has received increasing attention as it has steadily become clear that mechanical signals play a central role not only in enabling cell behaviours like migration and mitosis, but also in integrating contextual information and triggering state changes like cellular differentiation or apoptosis. (royalsocietypublishing.org)
- The eight-gene signature features the cancer hallmark epidermal growth factor receptor (EGFR) and genes involved in cell adhesion, migration, invasion, tumor growth and progression. (biomedcentral.com)
- Dynamic macromolecule assemblies called focal adhesions form at the cell:cell and cell:extracellular matrix (ECM) junctions, and it is their constant state of assembly and disassembly that mediates cell adhesion, proliferation, migration, and a host of other critical cell functions. (thermofisher.com)
- During retinal development, cell-cell and cell-ECM interactions are necessary for cell adhesion, migration, proliferation, and differentiation and are likely to be critical in establishing the highly organized architecture of the retina. (wiley.com)
- the intestinal epithelial integrity is maintained by continuous replacement of epithelial cells through a stereotyped cycle of cell proliferation, migration, differentiation, and apoptosis ( 10 , 23 , 30 , 44 ). (physiology.org)
- Furthermore, ablation of paxillin-PABP1 association impeded a number of indices of cell motility including spreading on fibronectin, cell migration on two-dimensional matrices, and transmigration in Boyden chambers. (asm.org)
- These data indicate that PABP1 must associate with paxillin in order to be efficiently transported from the nucleus to the cytoplasm and that this event is necessary for cells to remodel their focal adhesions during cell migration. (asm.org)
- essential for cell survival, migration and angiogenesis. (ahajournals.org)
- Interestingly, rhLK8 showed antiangiogenic effect, particularly on fibronectin-mediated migration of endothelial cells. (diabetesjournals.org)
- A cryptic apolipoprotein(a) kringle domain, containing kringle IV-9, IV-10, and V, also suppressed migration of endothelial cells and angiogenesis-dependent tumor growth ( 11 ). (diabetesjournals.org)
- Interestingly, rhLK8 inhibited the migration of endothelial cells mediated by FN, not collagen or vitronectin (VN). (diabetesjournals.org)
- Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. (uniprot.org)
- c-Src contributes to the regulation of both focal adhesions (cell-matrix interactions) and adherens junctions (cell-cell interactions), which are essential mediators of cell adhesion, migration, and invasion. (aacrjournals.org)
- Coordinated shifts of actin cytoskeleton and cell adhesion go along with maturation of lymphoid cells their migration through lymphoid organs also to sites of inflammation aswell as metastasis of changed cells. (exposed-skin-care.net)
- Key phrases: lymphocytes paxillin actin Rac1 RhoA LFA-1 PKC-δ Intro Lymphocyte migration takes on a key part in a multitude of physiological procedures. (exposed-skin-care.net)
- Changes in LFA-1 activity occur during lymphocyte maturation during SNX-2112 the immune response which often entails migration through tissues to sites of inflammation as well as during metastasis of transformed cells. (exposed-skin-care.net)
- Lunasin caused an increase in the expression of the inhibitor of kappa B alpha, a decrease in nuclear p50 NF-kB and a reduction in the migration of cancer cells. (nanohub.org)
- Prostatic carcinoma cell migration via alpha(v)beta3 integrin is modulated by a focal adhesion kinase pathway. (semanticscholar.org)
- Subsequently, we found that MUC1/ICAM-1 binding results in pro-migratory calcium oscillations, cytoskeletal reorganization, and simulated transendothelial migration. (biomedcentral.com)
- We then report that MUC1 forms constitutive cytoplasmic domain dimers which are necessary for Src recruitment, ICAM-1 induced calcium oscillations and simulated transendothelial migration. (biomedcentral.com)
- Our data implicates non-cysteine linked MUC1 dimerization in cell signalling pathways required for cancer cell migration. (biomedcentral.com)
- We have been investigating the mechanism of cell migration in the Luminal B breast cancer cell lines MCF7 and T47D, and were the first to demonstrate that MUC1 mediates heterotypic cell-cell adhesion by binding ICAM-1 [ 4 ], which is expressed on peritumoral stromal and endothelial cells. (biomedcentral.com)
- Oncogenic forms of the non-receptor tyrosine kinase Src alter cell structure, in particular the actin cytoskeleton and the adhesion networks that control cell migration, and also transmit signals that regulate proliferation and cell survival. (biologists.org)
- These studies also shed light on the role of focal adhesion kinase (FAK) downstream of v-Src and other signalling pathways in controlling migration, invasion and survival of transformed cells. (biologists.org)
- Calpains are calcium dependent cysteine proteases, which control the podocyte cytoskeleton, cell adhesion and motility via cleavage of paxillin, focal adhesion kinase and talin. (bristol.ac.uk)
- Paxillin has been found to play an important role in cell differentiation, and its phosphorylation is regulated by NO in cultured SMCs. (ahajournals.org)
- Paxillin is highly expressed in smooth muscle cells (SMCs) and is localized in dense plaques in vivo and at focal adhesion sites, the homologue of dense plaque, in cultured cells. (ahajournals.org)
- 14 Rhombotin-2 is required for erythroid differentiation during mouse development, 15 and paxillin has also been found to be associated with the differentiation of HL-60 and neuronal cells. (ahajournals.org)
- Fibronectin increases association of FAK with integrin α5β1, Paxillin, Actin, ERK, PI3K and localization at Focal Adhesion sites. (scirp.org)
- At least one pathway by which this occurs seems to involve focal adhesion kinase (FAK) and Src activation ( 2 ) and paxillin ( 6 , 7 ) and has been shown to be active in breast ( 8 ), head and neck ( 6 ), and colon ( 1 ) cancer cell lines, as well as in primary human colon cancer cells isolated directly from surgical specimens ( 2 ). (aacrjournals.org)
- The GRB2 binding can displace Paxillin from its binding sites on the FAK1, and Tyr925-phosphorylated FAK1 might be selectively released from the focal contacts. (bio-rad.com)
- Expression of nuclear-localized paxillin LIM domains stimulate DNA synthesis and cell proliferation. (biochemj.org)
- By real-time PCR analysis we have established that overexpression of either full-length paxillin or a truncated nuclear form suppresses expression of the parental imprinted gene H19, and modulation of this locus probably affects the rate of NIH-3T3 cell proliferation. (biochemj.org)
- On the other hand, the FA disassembly in FAK -/- cells was significantly impaired, as the rate constants for the disassembly of paxillin and zyxin were about 14-fold less in FAK -/- cells compared to wild-type cells. (hindawi.com)
- When FAK was reintroduced in FAK -/- cells, the rate constant for paxillin disassembly was comparable to that observed for wild-type cells [ 6 ]. (hindawi.com)
- This isotropic spreading was induced by the ability of kindlin to directly bind paxillin, which in turn bound focal adhesion kinase (FAK) resulting in FAK activation and the formation of lamellipodia. (elifesciences.org)
- Kindlin and paxillin then work together to activate other signaling molecules to induce the cell spreading. (elifesciences.org)
- Anchorage-independent transformation induced by BE6 required both paxillin and BE6-binding LD motifs on paxillin but was independent of the major tyrosine phosphorylation sites of paxillin. (asm.org)
- The essential role of paxillin in transformation by BE6 highlights the role of paxillin in the transduction of cellular signals that result in anchorage-independent cell proliferation. (asm.org)
- The carboxy terminus of paxillin contains four LIM domains: LIM2 and -3 localize paxillin to focal adhesions ( 5 , 32 ), and LIM1, -2, and -3 support the tyrosine phosphorylation of FAK in ES cells ( 32 ). (asm.org)
- In the present study, we demonstrate through the use of paxillin-null mouse fibroblasts that both paxillin and BE6-binding sites on paxillin are required for the transformation by BE6. (asm.org)
- In contrast, talin and paxillin remained localized to focal adhesions, suggesting that activation of PI 3-kinase induced a restructuring of the plaque rather than complete dispersion. (rupress.org)
- By targeting the paxillin-binding subdomain sequences in PABP1, we have generated mutants of PABP1 that do not bind to cellular paxillin. (asm.org)
- The LIM domains contain information for targeting paxillin to focal complexes and can bind directly to tubulin ( 9 ). (asm.org)
- Moreover, the paxillin-PABP1 complex undergoes nucleocytoplasmic shuttling and is localized to sites of translation in the perinuclear endoplasmic reticulum and at the leading edge of migrating cells ( 29 ). (asm.org)
- None of the residues in this loop are directly involved with the coordination of mRNA, making it an excellent candidate for a functional paxillin-binding site. (asm.org)
- Mutation analysis showed that co-localization was dependent on the paxillin-binding domain of GIT1. (ahajournals.org)
- Rearrangements of actin cytoskeleton that result in the cell's acquisition of a spherical form and LFA-1 activation are accomplished upon activation of PKC-δ that binds and straight phosphorylates paxillin at threonine (T) 538 with consequent RhoA activation. (exposed-skin-care.net)
- Binding of CRP with integrin α2 leads to the activation of focal adhesion kinase (FAK), paxillin and ERKs. (elsevierpure.com)
- CRP also binds to an Fcγ 3 receptor Fcγ 3 receptor I (Fcγ 3RI), and induces activation of paxillin, FAK and ERKs. (elsevierpure.com)
- Involvement of CRP in adhesion, invasion, anchorage-independent growth and upregulation of integrin α2, paxillin and FAK was observed in MDA-MB-231 triple-negative human breast cancer (TNBC) cells. (elsevierpure.com)
- It is believed that integrin-dependent autophosphorylation of FAK recruits and activates Src family kinases, which in turn trigger downstream signaling events. (pnas.org)
- The downstream S6 kinase is not involved, however, because rapamycin does not block the effect. (aacrjournals.org)
- Integrin-mediated p130Cas/BCAR1 phosphorylation upon adhesion to extracellular matrix (ECM) induces downstream signaling that is required for allowing cells to spread and migrate on the ECM. (wikipedia.org)
- Tyrosine 397 is an autophosphorylation site of FAK and is a critical component in downstream signaling ( 7 ), providing a high-affinity binding site for the SH2 domain of Src family kinases ( 8 , 9 ). (aacrjournals.org)
- Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G(1) phase as a downstream target of focal adhesion kinase (FAK). (genecards.org)
- Meanwhile, we present evidence that GPR56 inhibits fibronectin deposition and its downstream signaling, such as phosphorylation of focal adhesion kinase (FAK), during this process. (frontiersin.org)
- We also demonstrate that C. jejuni activates FAK autophosphorylation activity at Y-397 and phosphorylation of Y-925, which is required for stimulating two downstream guanine exchange factors, DOCK180 and Tiam-1, which are upstream of Rac1. (frontiersin.org)
- These results indicate that impairing COX-1 and COX-2 and their downstream effect by targeting ET A R can be therapeutically advantageous in ovarian carcinoma treatment. (aacrjournals.org)
- However, the downstream mediators of the Raf-1/MEK1/2/ERK/1/2 signaling cascade are unknown. (aacrjournals.org)
- In the present study, we show that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade in BON cells. (aacrjournals.org)
- Our previous studies have shown that polyamine depletion stabilizes p53, resulting in inhibition of intestinal epithelial cell (IEC) proliferation, but the exact downstream targets of induced p53 are still unclear. (physiology.org)
- Furthermore, our results showed high binding affinity of rhLK8 to α3β1 integrin and downstream inhibition of activation of FAK, p130 Crk-associated substrate (p130CAS), and c-Jun NH 2 -terminal kinase (JNK). (diabetesjournals.org)
- The activation of OsMKK1 and its downstream kinase OsMPK1 is dependent on Thr-25 phosphorylation of OsMKK1 in ABA signaling. (bvsalud.org)
- The interaction between c-Src and its substrate focal adhesion kinase (FAK) is essential for normal focal adhesion turnover as well as downstream signaling, which can regulate metalloproteinase production required for cancer cell invasion. (aacrjournals.org)
- In pancreatic cancer cells, activation of c-Src led to downstream activation of signal transducers and activators of transcription 3 (STAT3), which binds to the VEGF promoter along with hypoxia-inducible factor-1α ( 12 ). (aacrjournals.org)
- In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2 /FAK and of the downstream kinases MAPK1 /ERK2 and MAPK3 /ERK1, and ultimately to the stimulation of sprouting angiogenesis. (sdsc.edu)
- In this paper, we analyze how phosphorylation of FAK regulates its trafficking at FAs in living human astrocytoma cells. (hindawi.com)
- Because GIT1 regulates signaling by several vascular smooth muscle cell (VSMC) growth factors, we hypothesized that intima formation would be inhibited by GIT1 depletion. (ahajournals.org)
- Recently, we have shown that activation of the Raf-1 pathway regulates cell-cell contact in medullary thyroid cancer cells ( 13 ). (aacrjournals.org)
- Furthermore, Ser-67 phosphorylation in ZmCCaMK regulates its Ca2+ /CaM binding, autophosphorylation and transphosphorylation activity, and positively affects its function in drought tolerance in maize. (bvsalud.org)
- Experiments after depletion of FAK through different techniques have shown its active participation in different cellular activities like cell attachment, cell survival and apoptosis, cell proliferation etc [4-6]. (scirp.org)
- Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. (proteopedia.org)
- Administration of the FAK inhibitor Y15 perturbed the proliferation of melanoma metastases, supporting a causative link between the cell adhesion defect induced by GPR56 and its inhibition of metastatic growth. (frontiersin.org)
- The ECM is a network of macromolecules between cells that forms a scaffold to support tissue structure, as well as retain moisture and growth factors necessary for cell survival and proliferation ( 3 , 5 , 6 ). (frontiersin.org)
- Curcumin is one of the promising chemopreventive and chemotherapeutic agents ( 11 ) and inhibits the proliferation of tumor cells in vitro ( 12 ), and suppressing tumor formation in various animal models ( 13 - 15 ). (aacrjournals.org)
- Quercetin is a flavonoid that can inhibit proliferation of tumor cells and reduce the number of aberrant crypt foci, although increase of number of colon tumors was also reported. (tudelft.nl)
- Also, cell proliferation and cell cycle distribution were measured. (tudelft.nl)
- Results: Quercetin (5 μM) downregulated expression of cell cycle genes (for example CDC6, CDK4 and cyclin D1), downregulated cell proliferation and induced cell cycle arrest in Caco-2 cells. (tudelft.nl)
- After exposure to 50 μM quercetin cell proliferation decreased to 51.3% of control, and further decrease of the percentage of cells in the G1 phase coincided with an increase of the percentage of cells in the sub-G1 phase. (tudelft.nl)
- Because normal epithelial architecture constrains abnormal cell proliferation ( 22 ), its disorganization by CagA may also contribute neoplastic transformation of cells. (pnas.org)
- In another study, we reported that RLPs induced smooth muscle cell (SMC) proliferation, independently of oxidative stress. (nii.ac.jp)
- Recently, we identified the molecular mechanisms, in which RLPs from hypertriglyceridemic patients stimulated SMC proliferation via epidermal growth factor (EGF) receptor transactivation and heparin-binding EGF-like growth factor (HB-EGF) shedding. (nii.ac.jp)
- Increased FAK expression has been correlated with the enhanced motility and invasiveness of human tumor cells, as well as with promoting increased cell proliferation (5). (novusbio.com)
- The phosphorylation of FAK's tyrosine and serine residues in response to integrin engagement, mitogenic neuropeptides, lysophosphatidic acid, platelet-derived growth factor, activated Rho, and selected oncogenes leads to the formation of docking sites for a variety of signaling molecules that ultimately regulate cell morphology, locomotion, proliferation, differentiation, and apoptosis [1-3]. (thermofisher.com)
- Normal intestinal mucosal growth requires polyamines that regulate expression of various genes involved in cell proliferation, growth arrest, and apoptosis. (physiology.org)
- It has been shown that normal IEC proliferation in the mucosa is dependent on the supply of polyamines to the dividing cells in the crypts and that decreasing cellular polyamines inhibits cell renewal in vivo as well as in vitro ( 24 , 44 - 46 ). (physiology.org)
- The activation of tyrosine kinases is the initial step in regulating a variety of cellular processes, including proliferation, differentiation, and inflammatory responses. (jneurosci.org)
- One potential therapeutic target, the non-receptor tyrosine kinase c-Src, causes changes in proliferation, motility, invasion, survival, and angiogenesis in cancer cells and may be a valid therapeutic target in MPM. (aacrjournals.org)
- The apparently opposing survival and apototic effects that v-Src can simultaneously induce in cells make it difficult to predict whether and, if so, how oncogenic Src influences survival signalling in cancer cells that have mutations in other proliferation and death pathways. (biologists.org)
- This causes an increase in tumor cell apoptosis and a decrease in tumor cell proliferation, in FACT-positive cancers. (cancer.gov)
- YopP- and Yersinia- , but not Salmonella -induced apoptosis was specifically prevented by transient overexpression of NF-κB p65, giving evidence that YopP mediates cell death by disrupting the NF-κB signaling pathway. (jimmunol.org)
- Transfection of J774A.1 macrophages with YopP induced a moderate, but significant degree of apoptosis (40-50% of transfected cells). (jimmunol.org)
- Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. (springer.com)
- We have studied the role of these two kinases in resistance to apoptosis. (aacrjournals.org)
- Colon cancer cell lines were more resistant to Ad-FAK-CD-induced detachment and apoptosis than the breast cancer cell line, BT474. (aacrjournals.org)
- Ad-FAK-CD-induced apoptosis was significantly increased by PP2, an inhibitor of Src family kinases. (aacrjournals.org)
- Activation of caspase-3, down-regulation of FAK, and Src and AKT activities were demonstrated in Ad-FAK-CD + PP2-treated colon cancer cells undergoing apoptosis. (aacrjournals.org)
- The results suggest that FAK and Src are both important survival factors, playing a role in protecting colon cancer cell lines from Ad-FAK-CD-induced apoptosis. (aacrjournals.org)
- Dual inhibition of these kinases may be important for therapies designed to enhance the apoptosis in colon cancers. (aacrjournals.org)
- Normal cells undergo apoptosis or "anoikis" when they lose adhesion to extracellular matrix (ECM) ( 1 , 2 ). (aacrjournals.org)
- FAK has been shown to become overexpressed in tumor cells ( 10 -14 ), providing survival signals that suppress apoptosis in human breast cancer cells ( 15 , 16 ). (aacrjournals.org)
- Furthermore, overexpression of a constitutively active form of FAK prevented apoptosis of epithelial cells ( 20 ). (aacrjournals.org)
- Similarly, microinjection of peptides impaired FAK-integrin binding and antibodies against FAK induced apoptosis ( 21 ). (aacrjournals.org)
- Finally, FAK has been shown to suppress etoposide and hydrogen peroxide-induced apoptosis in HL-60 cells ( 22 ) as well as chemically induced apoptosis in renal epithelial cells ( 23 ). (aacrjournals.org)
- Thus, FAK can suppress apoptosis in a number of different cellular systems, although the molecular mechanisms of apoptotic resistance in human cancer cells remain unclear ( 15 ). (aacrjournals.org)
- In the present study, we studied apoptosis induced by FAK down-regulation in colon cancer cell lines and found them more resistant than other human breast cancer cell lines that we have studied ( 15 , 19 ). (aacrjournals.org)
- Because many colon cancer cells overexpress both Src and FAK, in contrast to breast cancer cell lines, we hypothesized that Src may contribute additional survival signals to the colon cancer cells to make them more resistant to apoptosis. (aacrjournals.org)
- We have shown that simultaneous inhibition of both Src and FAK caused increased apoptosis in colon cancer cell lines. (aacrjournals.org)
- Thus, FAK and Src overexpression provide protection of colon cancer cell lines from apoptosis. (aacrjournals.org)
- We have previously shown that different breast cancer cell lines overexpress FAK detachment and undergo apoptosis after down-regulation of p125 FAK expression by adenoviral delivery of a dominant-negative COOH-terminal FAK construct, Ad-FAK-CD ( 15 , 19 ). (aacrjournals.org)
- Focal adhesion kinase (FAK) is thought to play a key role in maintaining focal adhesion function and cell survival, whereas caspase-mediated FAK proteolysis is implicated in focal adhesion disassembly during apoptosis. (portlandpress.com)
- We examined the relationship between changes in FAK phosphorylation and proteolysis during apoptosis of primary porcine aortic endothelial cells (PAEC) induced by staurosporine, a widely used apoptogenic agent in diverse cell types. (portlandpress.com)
- Staurosporine-induced PAEC apoptosis was detected after 1h and was preceded by disruption and loss of FAK localization to focal adhesions within a few minutes, whereas staurosporine-induced cleavage of FAK occurred only after 8-24h. (portlandpress.com)
- These studies show that FAK dephosphorylation and focal adhesion disassembly are very early events mediating the onset of staurosporine-induced endothelial cell apoptosis and are dissociated from FAK proteolysis. (portlandpress.com)
- Par-4 induces apoptosis specifically in some cancer cells, but not in normal or immortalized cells. (nature.com)
- Par-4 was originally identified in rat prostate cancer cells undergoing apoptosis 1 . (nature.com)
- Differentially expressed genes were categorized in seven functional groups: cell cycle and differentiation, apoptosis, tumor suppressor genes and oncogenes, cell adhesion and cell-cell interaction, transcription, signal transduction and energy metabolism. (tudelft.nl)
- We have been studying a basement membrane-derived angiogenesis inhibitor called tumstatin, which selectively stimulates apoptosis of endothelial cells ( 5-8 ). (sciencemag.org)
- Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. (abcam.com)
- In apoptosis, the binding of FAK1 to RIPK1 and PI3K can induce survival signals, but the cleavage of FAK1 by Caspase 3 (or Calpain) is associated with death signaling and membrane formation during blebbing. (biolegend.com)
- Although several potential mechanisms have been suggested, including oxidative stress, mitochondrial dysfunction, cytotoxicity, and cell apoptosis [ 7 - 10 ], the exact mechanism remains unknown. (molvis.org)
- p53 loss not only prevents incipient tumor cells from undergoing oncogene-induced senescence and apoptosis, but also perturbs cell-cycle checkpoints. (aacrjournals.org)
- In this tumor, the ET-1/ET A R autocrine pathway promotes mitogenesis, apoptosis protection, invasion, and neoangiogenesis. (aacrjournals.org)
- However, overexpression of NDRG1 failed to directly induce cell death and to alter susceptibility to apoptosis induced by tumor necrosis factor-α/cycloheximide. (physiology.org)
- Undifferentiated epithelial cells continuously replicate in the proliferative zone within crypts and differentiate as they migrate up the villous tips, where differentiated cells are removed by apoptosis a few days later ( 10 , 30 , 33 ). (physiology.org)
- The p53 gene is implicated in regulation of the cell cycle, apoptosis, and the onset of cellular senescence ( 5 , 8 , 42 ), thus playing a critical role in the negative control of normal intestinal mucosal growth ( 11 , 16 , 17 ). (physiology.org)
- Three of the four cell lines were sensitive by in vitro cytotoxicity assays to the c-Src inhibitor dasatinib, which led to cell cycle arrest and increased apoptosis. (aacrjournals.org)
- Cis -diamminedichloroplatinum(II) (cisplatin)-induced renal proximal tubular apoptosis is known to be preceded by actin cytoskeleton reorganization, in conjunction with disruption of cell-matrix and cell-cell adhesion. (aspetjournals.org)
- In the present study, we show that the proinflammatory cytokine tumor necrosis factor α (TNF- α ) aggravated these cisplatin-induced F-actin and cell adhesion changes, which was associated with enhanced cisplatin-induced apoptosis of immortalized proximal tubular epithelial cells. (aspetjournals.org)
- Pharmacological inhibition of Rho kinase signaling re-established the synergistic apoptosis induced by combined cisplatin/TNF- α treatment of shRelB cells. (aspetjournals.org)
- In conclusion, our study shows for the first time that RelB is required for the cisplatin/TNF- α -induced cytoskeletal reorganization and apoptosis in renal cells by controlling a Rho kinase-dependent signaling network. (aspetjournals.org)
- TRPC6-/- podocytes are less motile and more adhesive, with an altered actin cytoskeleton compared to wild type cells. (bristol.ac.uk)
- Knockdown or expression of the truncated K874*, but not the gain of function G019S or dominant negative mutant of TRPC6 results in the mislocalization of calpain 1 and 2 and significant down-regulation of calpain activity leading to altered podocyte cytoskeleton, motility and adhesion, a phenocopy of TRPC6 -/- podocytes. (bristol.ac.uk)
- An intact cytoskeleton seems to be required for FAK activation and the ultimate effect on adhesion ( 10 ), so the cytoskeleton may act as a tensegrity style sensor for external forces that activate this pathway. (aacrjournals.org)
- An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. (prezi.com)
- A major role of FAK is to influence the dynamic regulation of integrin-associated adhesions, and the actin cytoskeleton that is tethered there, through diverse molecular interactions. (hindawi.com)
- These sites of adhesion provide the linkages to transduce forces generated by the cytoskeleton that drive axonal outgrowth and shape, developing synaptic specializations ( Suter and Miller, 2011 ). (biologists.org)
- To investigate the effect of elevated hydrostatic pressure on the expression and distribution of zonula occludens-1 (ZO-1), and its effect on cytoskeleton and focal adhesion in immortal human trabecular meshwork cells (iHTM) and glaucomatous human trabecular meshwork cells (GTM 3 ). (molvis.org)
- Actin cytoskeleton and focal adhesion (vinculin) were also assessed by immunofluorescence. (molvis.org)
- Sustained pressure elevation may directly damage trabecular meshwork cells by injuring ZO-1, cytoskeleton, and foal adhesions. (molvis.org)
- v-Src and Src are known to modulate the actin cytoskeleton and cell adhesion structures from their peripheral sites of activity (reviewed by Frame, 2002 ). (biologists.org)
- 21-24 The importance of Fak to the regulation of early gene transcription in response to stretch was demonstrated in neonatal rat cardiac myocytes, 20 indicating that this kinase may coordinate signaling pathways involved in the hypertrophic growth induced by mechanical stress. (ahajournals.org)
- Binding to the ECM is regulated by various signaling pathways that control the assembly and disassembly of three distinct, but functionally related actin and integrin-containing adhesion structures known as focal adhesions, podosomes, and invadopodia. (hindawi.com)
- Among its related pathways are Signaling events mediated by focal adhesion kinase . (genecards.org)
- Interactions between cells and the extracellular matrix coordinate signaling pathways that control various aspects of cellular behavior. (biologists.org)
- To gain further insight into alterations in cellular pathways, tumor profiling, and marker discovery in colorectal cancer (CRC) we used a new antibody microarray specific for cell signaling. (mcponline.org)
- Rho participates in signaling pathways that lead to the formation of actin stress fibers and focal adhesions ( 2 ). (sciencemag.org)
- The CK8/CK18 complex modulates the signaling pathways intracellularly by binding kinases involved in signal transduction. (biomedcentral.com)
- These findings implicate a role for alpha3beta1 integrin and the associated signaling pathways in HHV-8 entry into the target cells. (jove.com)
- The present study elucidates a critical molecular basis between CRP, integrin α2 and Fcγ 3RI pathways in MCF10A breast cells and MDA-MB-231 TNBC cells, thereby providing useful information on CRP-induced aggressiveness of breast cells in the inflammatory microenvironment. (elsevierpure.com)
- The substrate domain consists of 15 repeats of the YxxP consensus phosphorylation motif for Src family kinases (SFKs). (wikipedia.org)
- Phosphorylation of FAK Tyr-397 creates a binding site for Src-family kinases, and phosphorylation of FAK Tyr-576/Tyr-577 in the kinase domain activation loop enhances catalytic activity (4). (novusbio.com)
- Src, the cellular counterpart of v-Src, is a member of a multigene family of membrane-associated non-receptor tyrosine kinases that comprises nine members, some of which (Src, Fyn and Yes) are ubiquitous and some of which display more-restricted expression (for a general review on Src-family kinases, including their structures and modes of regulation, see Thomas and Brugge, 1997 ). (biologists.org)
- Tyrosine Kinase Inhibitors and Signal Transduction Modulators: Rationale and Current Status as Chemopreventive Agents for Prostate Cancer. (springer.com)
- The results suggest therefore that the biological functions attributed to the association of Zap70 with Vav following T cell activation may equally reflect the association of Zap70 with CrkII, and further support a regulatory role for CrkII in the TCR-linked signal transduction pathway. (jimmunol.org)
- These novel findings suggest a model in which CK8, together with uPA, plasminogen and fibronectin, constitutes a signaling platform capable of modulating cell adhesion/growth-dependent signal transduction in breast tumor cells. (biomedcentral.com)
- Increasing evidence suggests that tumor cells can regulate their own adhesion via intracellular signals that modulate integrin binding affinity. (aacrjournals.org)
- Na(+)-K(+)-ATPase inhibition caused a sustained increase in the intracellular Ca(2+) concentration that obscured Ca(2+) transients observed in untreated cells during attachment. (nih.gov)
- These results suggest that the level of Na(+)-K(+)-ATPase activity strongly influences cell attachment, possibly by an effect on intracellular Ca(2+). (nih.gov)
- The α-chain is extracellular, whereas the β-chain traverses the cell membrane and contains the intracellular tyrosine kinase ( 1 ). (aacrjournals.org)
- It recognizes and binds its ligands intracellular adhesion molecules 1 2 and 3 (ICAM-1 2 3 Leukocytes circulating in the bloodstream express inactive LFA-1 that is unable to bind to the ligands. (exposed-skin-care.net)
- To investigate the mechanism by which the VEGF pathway coordinates with integrin αvβ5 and Src kinase, an in vivo angiogenesis model was used with a defined growth factor input, (i.e. (rupress.org)
- Although the full pathway has not yet been elucidated, the effects of pressure seem likely to require cytoskeletal mechanosensing, Src, phosphatidylinositol 3-kinase, focal adhesion kinase, and Akt-1 activation. (aacrjournals.org)
- This pathway may be a promising target for manipulation to inhibit metastatic cancer cell adhesion. (aacrjournals.org)
- Elements of the phosphatidylinositol 3-kinase (PI3K) pathway are known to be overexpressed in some malignancies and to influence cell adhesion and motility in other settings. (aacrjournals.org)
- Thus, the search for further elements in the pathway that mediates pressure-stimulated cancer cell adhesion led us to investigate whether signal elements of the PI3K pathway might play a role in mediating the effects of pressure on cancer cell adhesion. (aacrjournals.org)
- This changed our view of the more proximal part of this signal pathway because we had previously postulated that FAK-397 autophosphorylation within focal adhesions was an early event in the pressure-induced pathway, which is required for subsequent FAK-Src interaction and FAK-576/577 phosphorylation by Src ( 2 ). (aacrjournals.org)
- Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells. (biomedsearch.com)
- 20 min) by the ubiquitin-proteasome pathway (1). (cellsignal.com)
- Likely to be the GTPase effector that links the Rho-related GTPases to the JNK MAP kinase pathway. (abcam.com)
- We previously found that platelet-derived growth factor (PDGF)-BB, the most potent mitogen and chemoattractant of VSMCs in vitro, induces TM expression in VSMCs through Src kinase and PI3-kinase/Akt/mTOR-dependent signaling pathway. (biomedcentral.com)
- The FAK signaling pathway influences many facets of normal cell function. (thermofisher.com)
- Upon administration, FB inhibitor LNP023 binds to FB and prevents the formation of the alternative pathway (AP) C3-convertase (C3bBb). (cancer.gov)
- Focal adhesion formation and turnover has been used as a model system for understanding the mechanisms of cellular adhesion. (hindawi.com)
- Consistent with the proposal that FAK modulates adhesion turnover, the number of adhesions that turned over in protrusive regions of FAK -/- cells was markedly less than in wild-type cells. (hindawi.com)
- Moreover, ERK/MAP kinase phosphorylation is necessary for calpain2 activation which leads to FA turnover, with the formation of the active complex consisting of at least ERK/MAP kinase and calpain2 being driven by the adaptor function of FAK [ 8 ]. (hindawi.com)
- These data suggest that an increase in cell turnover in the small intestine, due to Sn2+, was responsible for these changes. (tudelft.nl)
- Although the precise role and the mechanism remain to be clarified, these emerging data implicate the MAPK signaling cascade in the control of focal adhesion formation and turnover required for cellular morphogenesis and motility. (aacrjournals.org)
- The rapid dynamic turnover rate of intestinal epithelial cells (IECs) is highly regulated and critically controlled by numerous factors, including cellular polyamines ( 24 , 41 ). (physiology.org)
- It has been also reported that FN induce FAK signaling in lung cancer cell line or mice model [9,10,20]. (scirp.org)
- Thus, Rho-kinase appears to mediate signals from Rho and to induce the formation of stress fibers and focal adhesions. (sciencemag.org)
- 1997). Therefore, we tested the ability of both of these ligands to induce polarization in peripheral T cell blasts. (nih.gov)
- Therefore, we propose a model in which DcR3.Fc may bind to and cross-link proteoglycans to induce monocyte adhesion. (ox.ac.uk)
- CagA-deregulated SHP-2 perturbs the Erk MAP kinase ( 15 ) and also dephosphorylates focal adhesion kinase (FAK) to induce an elongated cell-shape known as the hummingbird phenotype ( 8 , 16 ). (pnas.org)
- These cells were extensively characterised via motility, detachment and calpain activity assays, immunofluorescence and confocal or Total Internal Reflection fluorescence (TIRF) microscopy, and western blotting. (bristol.ac.uk)
- In addition, cells plated on soft substrates showed both increased motility ( 27 ) and decreased growth ( 26 ). (pnas.org)
- We hypothesize that regulation of Rac activity by tension may be important for motility, polarization, and directionality of cell movement. (rupress.org)
- Rho also participates in the regulation of cell morphology ( 3 ), cell aggregation ( 4 ), cell motility ( 5 ), cytokinesis ( 6 ), and smooth muscle contraction ( 7 ). (sciencemag.org)
- While much effort has appropriately been recently placed on understanding the molecular basis of adhesion and signaling mechanisms involved in cell motility, it is important to keep in mind that these processes occur in the context of a complex and changing wound environment, which includes soluble and insoluble (i.e., density) gradients of cell motility-promoting components. (springer.com)
- Modification of focal adhesion structure by PI 3-kinase and its lipid product, PtdIns (3,4,5)-P 3 , has important implications for the regulation of cellular adhesive strength and motility. (rupress.org)
- Recently, actin-rich structures, whose assembly is regulated by c-Src, termed podosomes, were found to contribute to tissue invasion, matrix remodeling and cell motility. (ahajournals.org)
- We find that VEGF-stimulated Src activity in chick embryo blood vessels induces the coupling of focal adhesion kinase (FAK) to integrin αvβ5, a critical event in VEGF-mediated signaling and biological responsiveness. (rupress.org)
- We have previously shown 20 that stretch induces Fak to cluster at myofilaments in neonatal rat ventricular myocytes, but no evidence linked Fak directly to costameres in such cells. (ahajournals.org)
- NGF activates Erk and EGR1, and induces p35 expression in PC12 cells (3). (cellsignal.com)
- Using interference reflection microscopy, we found that activation of phosphoinositide 3-kinase (PI 3-kinase) by PDGF induces the dissipation of focal adhesions. (rupress.org)
- Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling. (elsevierpure.com)
- As a result of Trop-2 expression, we also observe activation of Src and FAK, known to occur upon β(1) -RACK1 interaction. (nih.gov)
- In summary, our data demonstrate that the transmembrane receptor Trop-2 is a regulator of PrCa cell adhesion to FN through activation of the β(1) integrin-RACK1-FAK-Src signaling axis. (nih.gov)
- Otherwise, experiments performed with dominant-negative Fak and specific pharmacological Src inhibitor confirmed that Fak activation is strictly dependent on phosphorylation of Tyr397 and cooperation with Src as has been shown in the focal adhesion site. (ahajournals.org)
- Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. (proteopedia.org)
- Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. (proteopedia.org)
- p130Cas/BCAR1 plays a role in cell transformation and cancer progression and alterations of p130Cas/BCAR1 expression and the resulting activation of selective signalling are determinants for the occurrence of different types of human tumors. (wikipedia.org)
- Both RTKs and integrin activation affect p130Cas/BCAR1 tyrosine phosphorylation and represent an efficient means by which cells utilize signals coming from growth factors and integrin activation to coordinate cell responses. (wikipedia.org)
- 1 Plasmin is implicated in the proteolysis of cell/cell contacts, cell/matrix contacts, matrix components, and in the activation of latent matrix bound growth factors. (bmj.com)
- Initial cell adhesion and spreading occurs in parallel with an inhibition of RhoA-GTP levels and the simultaneous activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42), which results in suppressed actomyosin contractility and enhanced actin-mediated protrusion ( Fig. 2 ). (biologists.org)
- Specifically, in the present study, we show that tyrosine phosphorylation of PKD2 at residue Y87 defines its localization to the focal adhesions and leads to activation. (elsevier.com)
- Treatment with Y-27632 or ML-7 that inhibits myosin phosphorylation and contractility increased lamellipodia through Rac activation and decreased cell polarization. (rupress.org)
- Liver tissues were analyzed for activation of early events critical for hepatocyte priming and subsequent cell cycle progression. (jove.com)
- DcR3.Fc has been shown to stimulate cell adhesion and to modulate cell activation and differentiation by triggering multiple signaling cascades that are independent of its three known ligands. (ox.ac.uk)
- Using high resolution scanning electron microscopy, GTPase pull-downs, G-LISA, and gentamicin protection assays we found that each of these host cell factors is indeed required for activation of the small Rho GTPase member Rac1 and maximal host cell invasion of this pathogen. (frontiersin.org)
- Small interfering (si) RNA studies further show that DOCK180 and Tiam-1 act cooperatively to trigger Rac1 activation and C. jejuni invasion. (frontiersin.org)
- Recruited to focal adhesions upon activation. (abcam.com)
- Tlymphocyte activation is dependent upon a sustained physical interaction of the TCR, with a peptide-bound MHC molecule on the surface of APCs. (jimmunol.org)
- Despite compromised integrin activation and adhesion, Mn 2+ enabled talin- but not kindlin-deficient cells to initiate spreading on FN. (elifesciences.org)
- Processes such as epithelial-mesenchymal transition (EMT) and the activation of proteases that degrade the basement membrane and extracellular matrix (ECM) have been implicated in the metastatic process ( 1 ). (aacrjournals.org)
- A) Yeast transfected with the angiostatin-Gal4 binding domain and BIG3-Gal4 activation domain grow under growth-restricted conditions (−Leu, −His, −Trp) and in the presence of 50 mM 3-amino-1, 2,4-triazol. (nih.gov)
- No growth was detected in yeast transfected with both the angiostatin-Gal4 binding domain and the Gal4 activation domain, or the Gal4 binding domain and the BIG3-Gal4 activation domain. (nih.gov)
- The p53-Gal4 binding domain and SV40LT-Gal4 activation domain were used as positive controls. (nih.gov)
- B) The table shows the activity of the nonselectable β-gal marker in yeast cells transfected with angiostatin-Gal4 binding and the BIG3-Gal4 activation domain and controls. (nih.gov)
- Activation of the endothelin A receptor (ET A R) by endothelin (ET)-1 is biologically relevant in several malignancies, including ovarian carcinoma. (aacrjournals.org)
- Further evidence demonstrated that activation of PI 3-kinase by PDGF induced a decrease in the association of α-actinin with the integrin β subunit, and that PtdIns (3,4,5)-P 3 could disrupt this interaction in vitro. (rupress.org)
- Src binding to FAK promotes increased Src kinase activity, and in turn, Src-mediated phosphorylation of FAK within the kinase domain activation loop at Tyr 576/577 is needed for maximal FAK-associated activity ( 10 ). (aacrjournals.org)
- 104:327-335) that proline-rich tyrosine kinase (Pyk2) plays a critical role in the activation of adherent human neutrophils, and allowed an analysis of individual Pyk2 domains not possible with chemical inhibitors. (rupress.org)
- Consistently, polyamine depletion-induced activation of the NDRG1-promoter was decreased when p53-binding sites within the NDRG1 proximal promoter region were deleted. (physiology.org)
- The product of the p53 gene is a transcription factor with a sequence-specific DNA binding domain in the central region and a transcriptional activation domain at the NH 2 terminus ( 11 ). (physiology.org)
- In this study we show that the monoclonal antibody that recognizes an epitope on the cytokeratin 8 (CK8) ectoplasmic domain (anti-CK MAb) inhibits plasminogen activation mediated by urokinase-type plasminogen activator (uPA) in MCF-7 and MCF-10A neoT cells. (biomedcentral.com)
- Plasminogen activation is promoted by tissue type plasminogen activator (tPA), which can bind to both components of the cytokeratin heterodimer, CK8/CK18. (biomedcentral.com)
- Furthermore, rhLK8 inhibited phosphorylation of focal adhesion kinase, resulting in suppression of activation of consequent p130CAS-Jun NH 2 -terminal kinase. (diabetesjournals.org)
- To test this hypothesis, we determined the effects of c-Src inhibition in MPM cell lines and examined c-Src expression and activation in tissue samples. (aacrjournals.org)
- c-Src activation is also required for epidermal growth factor receptor (EGFR)-induced VEGF production in pancreatic tumor cells ( 13 ). (aacrjournals.org)
- Further, HHV-8 infection induced the integrin-mediated activation of focal adhesion kinase (FAK). (jove.com)
- Lunasin inhibited the activation of focal adhesion kinase by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human colon cancer cells, respectively. (nanohub.org)
- In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. (sdsc.edu)
- Inhibiting the interaction of cMET and IGF-1R with FAK effectively reduces growth of pancreatic cancer cells in vitro and in vivo. (nih.gov)
- Among these binding partners, PAK1 and FAK are known to regulate endothelial cell (EC) function in vitro , and contribute to angiogenesis in vivo [ 18 - 20 ]. (pubmedcentralcanada.ca)
- The behavior of melanoma cells has traditionally been studied in vitro in two-dimensional cell culture with cells adhering to plastic dishes. (mdpi.com)
- The term BM stromal cells is also used to describe the adherent cell population established from the in vitro culture of BM, and the predominant cell present in such an adherent cell population is generally the adventitial reticular/fibroblast-like cell. (springer.com)
- Dittel, B. N. and LeBien, T. W. (1995) Reduced expression of vascular cell adhesion molecule-1 on bone marrow stromal cells isolated from marrow transplant recipients correlates with a reduced capacity to support human B lymphopoiesis in vitro. (springer.com)
- We report the nuclear and optical in vitro and in vivo imaging of SKOV-3 cells by targeting HER2 with a bimodal trastuzumab conjugate. (stanford.edu)
- This construct was radiolabeled and used to image cellular binding and antibody uptake in vitro and in vivo. (stanford.edu)
- On the other hand, in vitro chemosensitivity experiments on cancer cell lines, such as the NCI-60 cell line panel, are helpful in elucidating the complex relationship between drug responsiveness and gene expression. (biomedcentral.com)
- We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complimentary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion and whole body glucose regulation. (diabetesjournals.org)
- Here, we show that OsDMI3, a rice (Oryza sativa) CCaMK, directly interacts with and phosphorylates OsMKK1, a MAPK kinase (MKK) in rice, in vitro and in vivo. (bvsalud.org)
- Using an in vivo invasion model and an orthotopic mouse tumor model with MDA-MB-231 cells, we showed that CRP has an important role in intravasation and tumor growth in vivo, demonstrating the in vivo relevance of our in vitro results. (elsevierpure.com)
- Inhibition of FAK and VEGFR-3 binding decreases tumorigenicity in neuroblastoma. (nih.gov)
- Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor-3 interaction leads to decreased survival in human neuroblastoma cell lines. (nih.gov)
- Here we have demonstrated, using COS cells that were untransfected or transfected with wild-type rat ouabain-resistant Na(+)-K(+)-ATPase, that partial inhibition of Na(+)-K(+)-ATPase has a dramatic influence on cell attachment to fibronectin. (nih.gov)
- Ouabain dose-dependently decreased attachment in untransfected cells and in cells expressing wild-type Na(+)-K(+)-ATPase, but not in cells expressing ouabain-insensitive Na(+)-K(+)-ATPase, whereas inhibition of Na(+)-K(+)-ATPase by lowering extracellular K(+) concentration decreased attachment in all three cell types. (nih.gov)
- Inhibition experiments support the hypothesis that the GTP-binding site of TG-2 is a potential binding site for endostatin. (biochemj.org)
- The effect of staurosporine was very potent with striking inhibition of Tyr 861 and Tyr 397 phosphorylation and focal adhesion disruption occurring in the range 10-100nM. (portlandpress.com)
- Significantly, curcumin-mediated inhibition of RON expression resulted in the blockade of RON ligand, MSP-induced invasion of breast cancer cells. (aacrjournals.org)
- With functional experiments, we also found that, in mutant KRAS NSCLC cells, FAK inhibition resulted in persistent DNA damage and susceptibility to exposure to IR. (aacrjournals.org)
- Suppression or pharmacologic inhibition of FAK causes DNA damage and radiosensitizing effects that promote the therapeutic effect of ionizing radiations both in cultured cells and in lung cancer xenografts. (aacrjournals.org)
- More subtly, it is possible that the clinical outcome of chemotherapy may hinge on the growth-inhibition of the more invasive cells rather than the less invasive cells in the neoplasm. (biomedcentral.com)
- The consequent inhibition of plasmin generation resulted in changed cell morphology, enhanced cell adhesion to fibronectin, reduced invasion potential, and an enhanced G1/S transition. (biomedcentral.com)
- The adventitial reticular cells line the abluminal surface of the marrow vascular sinus, and the cytoplasmic processes that extend from these cells are in direct contact with lymphohematopoietic cells (2) . (springer.com)
- Among the earliest detectable effects in engaged T cells are the phosphorylation of multiple cellular substrates on tyrosine residues, including the cytoplasmic tails of the TCR subunits ( 3 , 4 , 5 ). (jimmunol.org)
- SignalSilence® ADAM9 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit ADAM9 expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. (cellsignal.com)
- Contact between cells that mediate the exchange of small molecules.3. (prezi.com)
- We have described the ability of RANTES to polarize peripheral blood T cells, such that the CCR5 receptor migrates to the cell's leading edge while the ICAM-1, ICAM-3/ CD43, CD44 molecules localize at the uropod (Nieto et al. (nih.gov)
- The transient assembly of functional molecular complexes in activated T cells enables the recruitment of enzymes and other effector molecules to specific compartments at the immunological synapse, thus activating a tightly regulated gene transcription program, which leads to cell differentiation and acquisition of effector function. (jimmunol.org)
- Additionally, I was also given the opportunity to assist in the development of a cell based High-Throughput Screen assay for the identification of small molecules with activity against cancer cell invasion. (stanford.edu)
- The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. (elsevierpure.com)
- At cell-cell contacts in quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. (sdsc.edu)
- This FAK/αvβ5 complex was also detected in epidermal growth factor-stimulated epithelial cells, suggesting a function for this complex outside the endothelium. (rupress.org)
- We treated immortalised, nontumorigenic human bronchial epithelial cells (cell line BEAS-2B) and primary normal human bronchial epithelial cells (HBEC) with IPDI, and then collected the conditioned culture media (IPDI-BEAS-2B-CM and IPDI-HBEC-CM, respectively), which was added to BSMCs. (biomedsearch.com)
- CagA also elicits junctional and polarity defects in epithelial cells by interacting with and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) independently of CagA tyrosine phosphorylation. (pnas.org)
- CagA disrupts tight junctions and causes the loss of apical-basolateral polarity in polarized epithelial cells by binding and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) ( 20 ). (pnas.org)
- Collectively, our results suggest that C. jejuni infection of host epithelial target cells hijacks a major fibronectin → integrin beta1 → FAK → DOCK180/Tiam-1 signaling cascade, which has a crucial role for Rac1 GTPase activity and bacterial entry into host target cells. (frontiersin.org)
- It is well recognized that the epithelial breast cancer cells commonly overexpress the IGF-I receptor while IGF-II is expressed by the tumor stroma. (springer.com)
- Although intestinal epithelial stem cells are not currently studied ex vivo, and no unique in vivo markers are available, they can be labeled with [ 3 H]thymidine or bromodeoxyuridine during early postnatal life or in regenerative mucosa after injury induced by irradiation ( 31 ). (physiology.org)
- 12 ] used a variety of techniques to demonstrate the ability of several isolates of Y. ruckeri to invade Chinook salmon embryo cell line (CHSE-214), fathead minnow epithelial cell line (FHM) and rainbow trout liver cell line (R1). (biomedcentral.com)
- This protective effect was associated with increased stress fiber formation, cell-matrix, and cell-cell adhesion in the shRNARelB (shRelB) cells during cisplatin/TNF- α treatment, mimicking an epithelial-to-mesenchymal phenotypic switch. (aspetjournals.org)
- The proximal tubular epithelial cells (PTECs) are the primary target. (aspetjournals.org)
- Specifically, Src-transformed cells display reduced numbers of bundled actin filaments and cellular contacts, particularly the integrin-associated focal adhesions of mesenchymal cells and cell-cell adhesions of epithelial cells, as well as inhibited gap junction communication between adjacent cells. (biologists.org)
- Activated Talin binds to Phosphatidylinositol-4,5-bisphosphate ( PI(4,5)P2) -producing enzyme Phosphatidylinositol phosphate kinase type I gamma ( PIPKI gamma ) and activates it. (bio-rad.com)
- The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumour blood vessels, which suggest important roles for their bidirectional signals in many aspects of cancer development and progression. (nih.gov)
- Ultimately, activated focal adhesion kinase accumulates at the membrane in association with β 1 -integrin heterodimers and may modulate integrin binding affinity. (aacrjournals.org)
- These stimuli triggers p130Cas/BCAR1 tyrosine phosphorylation and its translocation from cytosol to the cell membrane. (wikipedia.org)
- Interestingly, membrane ruffling, tight engulfment of bacteria and invasion were only seen during infection of WT control cells, but not in fibronectin −/− , integrin beta1 −/− , and FAK −/− knockout cell lines. (frontiersin.org)
- Loss of this close apposition between the cell membrane and the extracellular matrix coincided with a redistribution of α-actinin and vinculin from the focal adhesion complex to the Triton X-100-soluble fraction. (rupress.org)
- Focal adhesions are the points of closest apposition between the cell membrane and the extracellular matrix substrate ( Izzard and Lochner 1976 ). (rupress.org)
- In contrast to previously published reports, we found that membrane proximal cysteine residues were not involved in dimerization or ICAM-1 induced signalling. (biomedcentral.com)
- The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins. (sdsc.edu)
- IAPs are commonly upregulated in cancer, and although initially thought to only regulate cell death, they are now known to be involved in many aspects of both normal tissue function and tumour development. (omicsonline.org)
- Furthermore, we focus special attention on the DNMTs' specificity for target sites, including key cis-regulatory factors such as CpG content, common motifs, transcription factors (TF) binding sites, lncRNAs, and histone marks to regulate DNA methylation. (bvsalud.org)
- Biological phenomena, such as cellular differentiation and phagocytosis, are fundamental processes that enable cells to fulfill important physiological roles in multicellular organisms. (sciencemag.org)
- This Review will focus on a subset of synthetic biology tools known as bottom-up techniques, which use technologies such as optogenetics and chemically induced dimerization to reconstitute cellular behavior in cells. (sciencemag.org)
- The diverse effector Yops act on different cellular levels to neutralize a multitude of host effector functions ( 1 ). (jimmunol.org)
- FAK operates at the contact points between tumor cells and the extra cellular matrix that surrounds them. (bio-medicine.org)
- There is also evidence which indicates that components of the urokinase system exert cellular effects independent of u-PA binding. (bmj.com)
- Host cell entry by the food-borne pathogen Campylobacter jejuni has been reported as one of the primary reasons of tissue damage in infected humans, however, molecular invasion mechanisms and cellular factors involved in this process are widely unclear. (frontiersin.org)
- This interaction results in a temporal and spatial organization of multiple cellular elements at the T cell-APC-contact region, referred to as the immunological synapse ( 1 , 2 ). (jimmunol.org)
- this interaction is required for cellular transformation by BE6 ( 1 , 30 ). (asm.org)
- Predictive numerical models of cellular response to biophysical cues have emerged as a useful quantitative tool for cell biology research. (royalsocietypublishing.org)
- In this perspective article we introduce a single cell model developed towards the design of novel biomaterials to elicit a regenerative cellular response for the repair of diseased tissues. (royalsocietypublishing.org)
- The model is governed by basic mechanisms of cell spreading (lamellipodial and filopodial extension, formation of cell-matrix adhesions, actin reinforcement) and is developed in the context of cellular interaction with functionalized substrates that present defined points of potential adhesion. (royalsocietypublishing.org)
- Since cellular mechanisms involve processes at the molecular level that render them unobservable in live cell experiments with most analytical techniques, numerous key aspects of cell behaviour remain unknown. (royalsocietypublishing.org)
- Modulation of the focal adhesion plaque provides a mechanism for the regulation of cellular adhesive strength. (rupress.org)
- IGFBP-1 can impact on cellular functions independently of IGF binding via an RGD (integrin binding) motif. (diabetesjournals.org)
- Integrin Alpha3beta1 (CD 49c/29) is a Cellular Receptor for Kaposi's Sarcoma-associated Herpesvirus (KSHV/HHV-8) Entry into the Target Cells Cell. (jove.com)
- It may be concluded that invasive potential of breast cancer cells may be modulated by regulation of FAK. (scirp.org)
- This is the first report showing the regulation of human RON gene expression by nuclear factor-κB and suggests a potential therapeutic role for curcumin in blocking RON tyrosine kinase-mediated invasion of carcinoma cells. (aacrjournals.org)
- The aim of our current study is to investigate the efficacy of curcumin on the regulation of RON tyrosine kinase in the invasive MDA-MB-231 and MDA-MB-468 cells. (aacrjournals.org)
- In budding yeast, RHO1 (a homolog of RhoA) is implicated in the regulation of cell morphology and budding ( 8 ). (sciencemag.org)
- The interaction of cancer cells with the tumor microenvironment plays a major role in the function and regulation of cancer cells and is therefore a critical determinant of the response of cancer cells to therapeutic agents [ 9 , 10 ]. (mdpi.com)
- Dorshkind, K. (1990) Regulation of hemopoiesis by bone marrow stromal cells and their products. (springer.com)
- Dittel, B. N., McCarthy, J. B., Wayner, E. A., and LeBien, T. W. (1993) Regulation of human B-cell precursor adhesion to bone marrow stromal cells by cytokines that exert opposing effects on the expression of vascular cell adhesion molecule-1 (VCAM-1). (springer.com)
- Furthermore, FAK-null cells showed impaired responses to decreases in substrate flexibility, which causes control cells to generate weaker traction forces and migrate away from soft substrates. (pnas.org)
- However, other aspects of F397-FAK cells, including the responses to substrate flexibility and the amplification of focal adhesions upon mechanical stimulation, were similar to that of control cells. (pnas.org)
- Focal adhesion kinase (FAK or pp125 FAK ) was first identified as a v- src substrate in chicken embryo fibroblasts ( 1 ). (pnas.org)
- So far, speculations have centered on the possible role of FAK in the detachment of cells from the substrate, as initially suggested by the apparent increase in the size of focal adhesions in FAK-null cells ( 21 ). (pnas.org)
- Additionally, p130Cas/BCAR1 tyrosine phosphorylation on its substrate domain can be induced by cell stretching subsequent to changes in the rigidity of the extracellular matrix, allowing cells to respond to mechanical force changes in the cell environment. (wikipedia.org)
- These adhesions are usually less dynamic and therefore capable of firm attachment to the substrate. (exposed-skin-care.net)
- Research studies have shown that ADAM9 is overexpressed in prostate cancer (5), pancreatic cancer (6), gastric cancer (7), and has been linked to invasion and metastasis in small cell lung cancer (8). (cellsignal.com)
- This is a rate-limiting step in metastasis because cells are often able to survive circulation and seed in distant organs, but are unable to proliferate into metastases ( 1 ). (frontiersin.org)
- Metastasis is a difficult and inefficient process, so cells that are able to survive and thrive in the new environment as metastases are especially difficult to eliminate. (frontiersin.org)
- Although these processes likely contribute to the ability of a tumor cell to exit its primary site and enter the circulation, the genes responsible for mediating these initial steps are likely not solely responsible for metastasis. (aacrjournals.org)
- Theoretically, this could contribute to the evolution of a cancer genome that is conducive to metastasis (step 1). (aacrjournals.org)
- Generation of plasmin is a characteristic of tumor cells, promoting the degradation of extracellular matrix, tumor progression and metastasis. (biomedcentral.com)
- Cell surface uPA, bound to uPA receptor (uPAR), activates plasminogen to plasmin, a central player in breast cancer progression and metastasis. (biomedcentral.com)
- Lunasin inhibited metastasis and potentiated the effect of oxaliplatin by reducing the expression of proliferating cell nuclear antigen. (nanohub.org)
- Lunasin inhibited metastasis by direct binding with alpha-5 beta-1 integrin suppressing FAK/ERK/NF-kB signaling, and potentiated the effect of oxaliplatin in preventing the outgrowth of metastasis. (nanohub.org)
- In the metastatic growth step, solitary cells proliferate to form small tumors called micrometastases, and after persistent growth the tumors develop vascular networks to promote their development into macrometastases ( 3 ). (frontiersin.org)
- Bovine Aortic Smooth Muscle Cells (BAOSMC) provide an excellent model system to study all aspects of cardiovascular function and disease, especially those related to mechanisms of hyperplasia and hypertrophy of intimal smooth muscle cells leading to vascular occlusion in atherosclerosis and stent restenosis. (cellapplications.com)
- Under inflammatory states, TM expression is drastically reduced in ECs while vascular smooth muscle cells (VSMCs) show a robust expression of TM. (biomedcentral.com)
- Thrombomodulin (TM), a transmembrane glycoprotein in endothelial cells (ECs), is a critical player in maintaining vascular thromboresistance. (biomedcentral.com)
- We previously reported that monocytes cultured in the presence of RLPs increased their adhesion to vascular endothelial cells. (nii.ac.jp)
- COX-2 inhibitors and, in part, COX-1 inhibitor blocked ET-1-induced PGE 2 and vascular endothelial growth factor release, indicating that both enzymes participate in PGE 2 production to a different extent. (aacrjournals.org)
- c-Src kinase activity is required for vascular endothelial growth factor (VEGF)-mediated angiogenesis ( 8 ). (aacrjournals.org)
- Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. (sdsc.edu)
- 7 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. (sciencemag.org)
- Unlike physiological forms of angiogenesis that occur during embryonic development and normal wound healing, pathological, tumor-induced angiogenesis often ensues due to imbalances in either angiogenic activators or inhibitors [ 1 , 3 ]. (pubmedcentralcanada.ca)
- FAK1 has also been shown to have roles in cell cycle progression and embryonic development. (biolegend.com)
- Using rat embryonic aorta-derived A7r5 VSMCs which do not express TM, the role of the chondroitin sulfate (CS) moiety of TM in VSMCs was delineated with cells expressing wild-type TM and the CS-devoid TM mutant. (biomedcentral.com)
- LD1 interacts with acropaxin and ILK ( 16 , 17 ), LD2 interacts with FAK and vinculin, LD4 interacts with GIT1 and FAK ( 29 ), and the LD3 and LD5 interaction partners remain uncharacterized, although LD5 is functionally required to support FAK tyrosine phosphorylation in embryonic stem (ES) cells ( 32 ). (asm.org)
- In addition to the β 1 subunit, β 3 and β 5 subunits have been identified in embryonic retina (Gervin et al. (wiley.com)
- DNMTs, along with other poorly studied elements, modulate the dynamic DNA methylation patterns of embryonic and adult cells. (bvsalud.org)
Localizes to focal1
- Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. (rcsb.org)
- Furthermore, ILK, but not vinculin or focal adhesion kinase, has been coisolated with PINCH from mammalian cells by immunoaffinity chromatography, indicating that PINCH and ILK associate with each other in vivo. (asm.org)
- When comparing iHTM with GTM 3 , the distribution of ZO-1 and vinculin in GTM 3 was not as regular as that in iHTM. (molvis.org)
- α-Actinin, vinculin, and talin are important structural components involved in the formation and stability of focal adhesions. (rupress.org)
- Ouabain reduced focal adhesion kinase autophosphorylation but had no effect on cell surface integrin expression. (nih.gov)
- Integrin clustering promotes FAK1 autophosphorylation at Tyr397, thereby creating a binding site for c-Src . (bio-rad.com)
- Signaling is modulated by ANGPT2 that has lower affinity for TEK , can promote TEK autophosphorylation in the absence of ANGPT1 , but inhibits ANGPT1 -mediated signaling by competing for the same binding site. (sdsc.edu)
- In cultured cells, zyxin is recruited to focal adhesions and stress fibers via C-terminal LIM domains and modulates cytoskeletal organization via the N-terminal domain. (biologists.org)
- These results suggest that Y. ruckeri can gain entrance into host cells through several mechanisms, and might take advantage of both the actin and microtubule cytoskeletal systems. (biomedcentral.com)
- Phosphorylation of Alpha-actinin by FAK1 reduces the crosslinking of stress fibers and prevents maturation of the focal contacts [ 5 ]. (bio-rad.com)
- At later phases, the activities of Rac1 and Cdc42 decrease, whereas the activity of RhoA gradually increases, which drives the formation of stress fibers and the maturation of focal adhesions. (biologists.org)
- The small guanosine triphosphatase (GTPase) Rho is implicated in the formation of stress fibers and focal adhesions in fibroblasts stimulated by extracellular signals such as lysophosphatidic acid (LPA). (sciencemag.org)
- Microinjection of the catalytic domain of Rho-kinase into serum-starved Swiss 3T3 cells induced the formation of stress fibers and focal adhesions, whereas microinjection of the inactive catalytic domain, the Rho-binding domain, or the pleckstrin-homology domain inhibited the LPA-induced formation of stress fibers and focal adhesions. (sciencemag.org)
- Involved in dissolution of stress fibers and reorganization of focal complexes. (abcam.com)
- As its name implies, the FAT domain is involved in directing FAK to focal adhesion complexes in a variety of cells [ 38 ]. (hindawi.com)
- which are transmitted to the ECM through integrin-containing adhesion complexes known as focal adhesions ( Burridge and Chrzanowska-Wodnicka, 1996 ). (biologists.org)
- Anti-gB antibodies immunoprecipitated the virus-alpha3 and -beta1 complexes, and virus binding studies suggest a role for alpha3beta1 in HHV-8 entry. (jove.com)
- In cardiomyocytes exposed to biomechanical stimulation, FAK accumulates in the nucleus, binds to and upregulates the transcriptional activity of MEF2 through an interaction with the FAK focal adhesion targeting (FAT) domain. (proteopedia.org)
- A CureFAKtor study reported earlier pinpointed the site of interaction of VEGFR-3 and FAK to create small molecule drugs capable of disrupting signaling and causing death of many types of cancer cells. (bio-medicine.org)
- This interaction requires phosphorylation of the Arp2/3 complex by p21-activated kinase 1 ( PAK1 ) that leads to polymerization of Actin [ 7 ]. (bio-rad.com)
- In this review, we summarize the existing knowledge on Par-4 tumor suppressive mechanisms, and discuss how the interaction of Par-4 with different regulators influence cell fate. (nature.com)
- Moreover, mutation of this residue blocks PKD2's interaction with Focal Adhesion Kinase (FAK). (elsevier.com)
- The PINCH-ILK interaction is mediated by the N-terminal-most LIM domain (LIM1, residues 1 to 70) of PINCH and multiple ankyrin (ANK) repeats located within the N-terminal domain (residues 1 to 163) of ILK. (asm.org)
- More recently, CagA was found to impair the cell-cell interaction independently of CagA tyrosine phosphorylation. (pnas.org)
- The work focuses on a subset of these mechanisms that regard interaction between cells and the extracellular matrix (ECM). (royalsocietypublishing.org)
- Interestingly, rhLK8 inhibited fibroblast growth factor (FGF)-stimulated phosphorylation of focal adhesion kinase (FAK), suggesting possible interference of rhLK8 in the interaction between ECM and endothelial cells. (diabetesjournals.org)
- We know that FAK protects tumors from chemotherapeutic drugs and radiation, allowing the tumor cells to resist these therapies. (bio-medicine.org)
- Studies by CureFAKtor and others found that in this role, FAK is an important facilitator for signals that cause tumor cells to survive, grow, and produce new blood vessels to sustain growth and travel to distant places within the body where they may establish new tumor sites. (bio-medicine.org)
- It also cocoons the tumor cells to protect them from the body's natural signaling mechanisms that would cause deviant tumor cells to be eliminated. (bio-medicine.org)
- This enables p53-deficient tumor cells with DNA damage to continue cycling, creating a permissive environment for the acquisition of additional mutations. (aacrjournals.org)
- The metastatic potential of tumor cells can be positively influenced by loss of p53 or expression of p53 gain-of-function mutants. (aacrjournals.org)
- The mechanisms by which tumor cells exit their primary site, intravasate into the bloodstream, extravasate into distal organs, and then establish growth in the secondary sites are not well understood. (aacrjournals.org)
- Like the drug-sensitivity heterogeneity, tumor cells often exhibit a wide range of invasion ability. (biomedcentral.com)
- Loss of gap junction intercellular communication is critical for tumor progression because it allows the tumor cells to escape growth control, invade, and metastasize. (aacrjournals.org)
- Vasculogenic mimicry is a hypoxia-activated process in which tumor cells form three-dimensional (3D) channel-like networks, resembling endothelial blood vessels, to obtain nutrients. (bvsalud.org)
- Anti-CK MAb, which competes for the binding site for uPA, could be used as an agent to reduce the invasive potential of breast tumor cells. (biomedcentral.com)
- Proteases are essential for invasion by tumor cells. (biomedcentral.com)
- With cell uptake much higher in tumor cells compared to normal cells, the F18 moiety of fluorodeoxygalactose F-18 can be visualized upon PET imaging and this agent can be used as a tracer for the evaluation of galactose tumor uptake and metabolism. (cancer.gov)
- F-18 16 alpha-fluoroestradiol is actively taken up in tumor cells expressing the estrogen receptor (ER), allowing visualization of ER-positive tumor cells with positron emiision tomography (PET). (cancer.gov)
- In addition, this agent is able to sensitize FACT-positive tumor cells to the cytotoxic effects of other chemotherapeutic agents. (cancer.gov)
Novel Focal Adhesi2
- CureFAKtor Pharmaceuticals Demonstrates Novel Focal Adhesion Kinase (FAK) Inhibitor C4 Analogs Inhibited Pancreatic Cancer Tumor Growth as Sin. (bio-medicine.org)
- CureFAKtor Pharmaceuticals Demonstrates that Novel Focal Adhesion Kinase (FAK) Inhibitors Decrease Pancreatic Cancer Tumor Blood Flow and Reduce Blood Vess. (bio-medicine.org)
- Using either shRNA-mediated silencing of Trop-2 in cells that endogenously express it, or ectopic expression of Trop-2 in cells that do not express it, we show that Trop-2 inhibits PrCa cell adhesion to fibronectin (FN). (nih.gov)
- Taken together, our results suggest that GPR56 in melanoma metastases inhibits ECM accumulation and adhesion, which contributes to its negative effects on metastatic growth. (frontiersin.org)
- Identification of a dendrimeric heparan sulfate-binding peptide that inhibits infectivity of genital types of human papillomaviruses" Antimicrobial Agents & Chemother. (unibs.it)
- Upon administration, CBL0137 binds to FACT and sequesters the FACT complex on chromatin, which inhibits its activity. (cancer.gov)
- it specifically inhibits the transcription of both NF-kappa β and heat shock transcription factor 1 (HSF1) and simultaneously activates p53. (cancer.gov)
- A FAK scaffold inhibitor disrupts FAK and VEGFR-3 signaling and blocks melanoma growth by targeting both tumor and endothelial cells. (nih.gov)
- Recombinant periostin restored the defects in cell morphology and matrix contraction displayed by periostin-deficient fibroblasts in a manner that was sensitive to a neutralizing anti-β1-integrin and to the FAK and Src inhibitor PP2. (biologists.org)
- Treatment of MDA-MB-231 cells with pyrrolidine dithiocarbamate, an inhibitor of p65, or small interfering RNA knockdown of p65, blocked RON gene expression and MSP-mediated invasion of MDA-MB-231 cells. (aacrjournals.org)
- These responses were inhibited in cells scrape-loaded with the Rho inhibitor C3 transferase. (ucl.ac.uk)
- As FAK -/- fibroblasts show excessive, rather than decreased, formation of focal contacts, FAK has been associated with the disassembly of integrin-based adhesion sites [ 5 ]. (hindawi.com)
- Taken together, these results show that FAK is necessary for the efficient disassembly of dynamic adhesions. (hindawi.com)
- 10 ) revealed that YopP/YopJ binds and inactivates members of the MAPK kinase superfamily, which function as upstream MAPK activators. (jimmunol.org)
- The MAPK cascade that activates ERK, c-Jun NH 2 -terminal kinase, and p38 kinases plays an important role in modifying the morphogenetic and motile responses of cells ( 12 ). (aacrjournals.org)
- The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. (cellsignal.com)
- Rho-kinase is composed of catalytic, coiled-coil, Rho-binding, and pleckstrin-homology domains. (sciencemag.org)
- FAK comprises a central catalytic domain flanked by a large NH 2 terminal domain containing the FERM region (band four point one, ezrin, radixin, and moesin) and a COOH terminal domain harboring the focal adhesion targeting sequence ( 7 ). (aacrjournals.org)
- The first part is a catalytic core region composed of an ATP binding site, which catalyses ATP hydrolysis  and a microtubule (MT) binding site, that tethers the motor to its MT track . (cytoskeleton.com)
- Tyrosine-phosphorylated CagA then specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase ( 9 , 14 ), a bona fide oncoprotein whose gain-of-function mutations are associated with human malignancies ( 13 ). (pnas.org)
- this promotes endothelial cell-cell adhesion. (sdsc.edu)
- RESULTS: For our study on FAK, we selected invasive Breast Cancer cell line MDA-MB-231 and treated the cells with Fibronectin (FN). (scirp.org)
- Fibronectin (FN) is one of the important ECM-glycolproteins which binds with Integrin. (scirp.org)
- The extracellular matrix (ECM) is an insoluble supra-structure comprised of a variety of matrix components including fibronectin, glycosaminoglycans, chrondronectin, osteonectin, collagens, laminin, proteoglycans, and growth factors [ 1 - 6 ]. (hindawi.com)
- To test this, we investigated the function of GPR56 on cell-fibronectin adhesion and its relationship with metastatic growth in melanoma. (frontiersin.org)
- Here we used knockout cell lines derived from fibronectin −/− , integrin beta1 −/− , and focal adhesion kinase (FAK) −/− deficient mice and corresponding wild-type (WT) controls, to study C. jejuni -induced signaling cascades involved in the bacterial invasion process. (frontiersin.org)
- The RGD integrin binding domain of IGFBP-1, through integrin engagement, focal adhesion kinase and integrin linked kinase enhanced insulin sensitivity and insulin secretion in C2C12 myotubes and INS-1 832/13 pancreatic beta cells. (diabetesjournals.org)
Loss of focal adhesions1
- Overnight culture of Swiss 3T3 cells in serum-free medium leads to loss of focal adhesions and associated actin stress fibres, although the cells remain well spread. (ucl.ac.uk)
- One potential therapeutic target is the Src family of nonreceptor tyrosine kinases (SFK), which are involved in multiple signaling cascades in cancer cells. (aacrjournals.org)
- Focal adhesion kinase (Fak) has been implicated as a signaling molecule involved in the early response of cardiac myocytes to mechanical stress. (ahajournals.org)
- Decoy receptor 3 (DcR3), a soluble receptor for Fas ligand, LIGHT (homologous to lymphotoxins shows inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes), and TNF-like molecule 1A, is highly expressed in cancer cells and in tissues affected by autoimmune disease. (ox.ac.uk)
- We were the first to report binding between MUC1 and Intercellular adhesion molecule-1 (ICAM-1), which is expressed on stromal and endothelial cells throughout the migratory tract of a metastasizing breast cancer cell. (biomedcentral.com)
- v-Src differs from Src by substitution of sequences at the C-terminus, which results in loss of amino acids that normally bind to the SH domains and stabilize the `closed' or inactive conformation of the molecule (reviewed by Frame, 2002 ). (biologists.org)
- Rho-kinase is activated by Rho and may mediate some biological effects of Rho. (sciencemag.org)
- When cells are stimulated with certain extracellular signals such as LPA, GDP·Rho is believed to be converted to GTP·Rho, which binds to specific targets that mediate its biological functions. (sciencemag.org)
- Upon binding to IGF-II, both IR-A and HRs may activate unique signaling patterns, which predominantly mediate proliferative effects. (springer.com)
- One hundred years later Perren and Pawel ( Perren 1979 ) hypothesized that cells mediate bone healing according to fluid flow and hydrostatic pressure. (royalsocietypublishing.org)
- Ligands that bind the Ret receptor include the glial cell line-derived neurotrophic factor (GDNF) and its congeners neurturin, persephin, and artemin (2-4). (cellsignal.com)
- Rho-kinase phosphorylates myosin light chain and thereby activates myosin adenosine triphosphatase (ATPase) ( 13 ). (sciencemag.org)
- and differentiation of mesenchymal cushion progenitor cells into contractile myofibroblasts ( Conway and Molkentin, 2008 ). (biologists.org)
- proposed quantitative models that predicted progenitor cell differentiation as functions of the nature of applied mechanical stimulus. (royalsocietypublishing.org)