Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.Cortactin: A microfilament protein that interacts with F-ACTIN and regulates cortical actin assembly and organization. It is also an SH3 DOMAIN containing phosphoprotein, and it mediates tyrosine PHOSPHORYLATION based SIGNAL TRANSDUCTION by PROTO-ONCOGENE PROTEIN PP60(C-SRC).Synaptophysin: A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.Perchlorates: Compounds that contain the Cl(=O)(=O)(=O)O- structure. Included under this heading is perchloric acid and the salts and ester forms of perchlorate.Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in MOLECULAR GENETICS to detect the presence of a complementary sequence by NUCLEIC ACID HYBRIDIZATION.Glass: Hard, amorphous, brittle, inorganic, usually transparent, polymerous silicate of basic oxides, usually potassium or sodium. It is used in the form of hard sheets, vessels, tubing, fibers, ceramics, beads, etc.Carbocyanines: Compounds that contain three methine groups. They are frequently used as cationic dyes used for differential staining of biological materials.Equidae: A family of hoofed MAMMALS consisting of HORSES, donkeys, and zebras. Members of this family are strict herbivores and can be classified as either browsers or grazers depending on how they feed.Nanodiamonds: Diamond nanoparticles that exhibit unique biological, thermal, mechanical, and optoelectronic properties. They have important NANOMEDICINE applications including DRUG DELIVERY SYSTEMS; DIAGNOSTIC IMAGING; protein separation; and BIOSENSING TECHNIQUES.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Proteins: 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.Sequence Analysis, Protein: A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.ArchivesAntibodies, Monoclonal: Antibodies produced by a single clone of cells.Influenzavirus A: A genus in the family ORTHOMYXOVIRIDAE causing influenza and other diseases in humans and animals. It contains many strains as well as antigenic subtypes of the integral membrane proteins hemagglutinin (HEMAGGLUTININS) and NEURAMINIDASE. The type species is INFLUENZA A VIRUS.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Abstracting and Indexing as Topic: Activities performed to identify concepts and aspects of published information and research reports.Information Storage and Retrieval: Organized activities related to the storage, location, search, and retrieval of information.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.Cell Adhesion: Adherence of cells to surfaces or to other cells.Actins: 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.Leukocyte Rolling: Movement of tethered, spherical LEUKOCYTES along the endothelial surface of the microvasculature. The tethering and rolling involves interaction with SELECTINS and other adhesion molecules in both the ENDOTHELIUM and leukocyte. The rolling leukocyte then becomes activated by CHEMOKINES, flattens out, and firmly adheres to the endothelial surface in preparation for transmigration through the interendothelial cell junction. (From Abbas, Cellular and Molecular Immunology, 3rd ed)Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.P-Selectin: Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.Selectins: Transmembrane proteins consisting of a lectin-like domain, an epidermal growth factor-like domain, and a variable number of domains that are homologous to complement regulatory proteins. They are important cell adhesion molecules which help LEUKOCYTES attach to VASCULAR ENDOTHELIUM.Chemotaxis, Leukocyte: The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.Polymerization: Chemical reaction in which monomeric components are combined to form POLYMERS (e.g., POLYMETHYLMETHACRYLATE).Actin Cytoskeleton: Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Data Mining: Use of sophisticated analysis tools to sort through, organize, examine, and combine large sets of information.Actin Depolymerizing Factors: A family of low MOLECULAR WEIGHT actin-binding proteins found throughout eukaryotes. They remodel the actin CYTOSKELETON by severing ACTIN FILAMENTS and increasing the rate of monomer dissociation.Microfilament Proteins: Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.Esophageal Neoplasms: Tumors or cancer of the ESOPHAGUS.Carcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Vascular Endothelial Growth Factor C: A vascular endothelial growth factor that specifically binds to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 and VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3. In addition to being an angiogenic factor it can act on LYMPHATIC VESSELS to stimulate LYMPHANGIOGENESIS. It is similar in structure to VASCULAR ENDOTHELIAL GROWTH FACTOR D in that they both contain N- and C-terminal extensions that were not found in other VEGF family members.Ribonuclease III: An endoribonuclease that is specific for double-stranded RNA. It plays a role in POST-TRANSCRIPTIONAL RNA PROCESSING of pre-RIBOSOMAL RNA and a variety of other RNA structures that contain double-stranded regions.Esophagectomy: Excision of part (partial) or all (total) of the esophagus. (Dorland, 28th ed)Vascular Endothelial Growth Factor D: A vascular endothelial growth factor that specifically binds to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 and VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3. In addition to being an angiogenic factor it can act on LYMPHATIC VESSELS to stimulate LYMPHANGIOGENESIS. It is similar in structure to VASCULAR ENDOTHELIAL GROWTH FACTOR C in that they both contain N- and C-terminal extensions that were not found in other VEGF family members.Cell Line, Tumor: A cell line derived from cultured tumor cells.Vascular Endothelial Growth Factors: A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells.Cell Surface Extensions: Specialized structures of the cell that extend the cell membrane and project out from the cell surface.Guanine Nucleotide Exchange Factors: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.Rho Guanine Nucleotide Exchange Factors: Signaling proteins which function as master molecular switches by activating Rho GTPases through conversion of guanine nucleotides. Rho GTPases in turn control many aspects of cell behavior through the regulation of multiple downstream signal transduction pathways.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.rho GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47.Proto-Oncogene Proteins c-vav: Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Matrix Metalloproteinase 14: A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN. Matrix metalloproteinase 14 plays a direct role in the cleavage of proteins in the pericellular environment. In addition, it can function indirectly by enzymatically activating the proprotein form of MATRIX METALLOPROTEINASE 15.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Pseudopodia: A dynamic actin-rich extension of the surface of an animal cell used for locomotion or prehension of food.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Wiskott-Aldrich Syndrome Protein, Neuronal: A member of the Wiskott-Aldrich syndrome protein family that is found at high levels in NERVE CELLS. It interacts with GRB2 ADAPTOR PROTEIN and with CDC42 PROTEIN.src-Family Kinases: 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.Adherens Junctions: 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.Cadherins: 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.Vinculin: A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10.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.alpha Catenin: A catenin that binds F-ACTIN and links the CYTOSKELETON with BETA CATENIN and GAMMA CATENIN.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Bone Resorption: Bone loss due to osteoclastic activity.Cell Membrane Structures: Structures which are part of the CELL MEMBRANE or have cell membrane as a major part of their structure.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.Receptor Activator of Nuclear Factor-kappa B: A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Cyclin-Dependent Kinase Inhibitor p57: A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Cyclin-Dependent Kinase Inhibitor Proteins: A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.

Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. (1/335)

Lymphocyte extravasation into the brain is mediated largely by the Ig superfamily molecule ICAM-1. Several lines of evidence indicate that at the tight vascular barriers of the central nervous system (CNS), endothelial cell (EC) ICAM-1 not only acts as a docking molecule for circulating lymphocytes, but is also involved in transducing signals to the EC. In this paper, we examine the signaling pathways in brain EC following Ab ligation of endothelial ICAM-1, which mimics adhesion of lymphocytes to CNS endothelia. ICAM-1 cross-linking results in a reorganization of the endothelial actin cytoskeleton to form stress fibers and activation of the small guanosine triphosphate (GTP)-binding protein Rho. ICAM-1-stimulated tyrosine phosphorylation of the actin-associated molecule cortactin and ICAM-1-mediated, Ag/IL-2-stimulated T lymphocyte migration through EC monolayers were inhibited following pretreatment of EC with cytochalasin D. Pretreatment of EC with C3 transferase, a specific inhibitor of Rho proteins, significantly inhibited the transmonolayer migration of T lymphocytes, endothelial Rho-GTP loading, and endothelial actin reorganization, without affecting either lymphocyte adhesion to EC or cortactin phosphorylation. These data show that brain vascular EC are actively involved in facilitating T lymphocyte migration through the tight blood-brain barrier of the CNS and that this process involves ICAM-1-stimulated rearrangement of the endothelial actin cytoskeleton and functional EC Rho proteins.  (+info)

Cell shrinkage regulates Src kinases and induces tyrosine phosphorylation of cortactin, independent of the osmotic regulation of Na+/H+ exchangers. (2/335)

The signaling pathways by which cell volume regulates ion transporters, e.g. Na+/H+ exchangers (NHEs), and affects cytoskeletal organization are poorly understood. We have previously shown that shrinkage induces tyrosine phosphorylation in CHO cells, predominantly in an 85-kDa band. To identify volume-sensitive kinases and their substrates, we investigated the effect of hypertonicity on members of the Src kinase family. Hyperosmolarity stimulated Fyn and inhibited Src. Fyn activation was also observed in nystatin-permeabilized cells, where shrinkage cannot induce intracellular alkalinization. In contrast, osmotic inhibition of Src was prevented by permeabilization or by inhibiting NHE-1. PP1, a selective Src family inhibitor, strongly reduced the hypertonicity-induced tyrosine phosphorylation. We identified one of the major targets of the osmotic stress-elicited phosphorylation as cortactin, an 85-kDa actin-binding protein and well known Src family substrate. Cortactin phosphorylation was triggered by shrinkage and not by changes in osmolarity or pHi and was abrogated by PP1. Hyperosmotic cortactin phosphorylation was reduced in Fyn-deficient fibroblasts but remained intact in Src-deficient fibroblasts. To address the potential role of the Src family in the osmotic regulation of NHEs, we used PP1. The drug affected neither the hyperosmotic stimulation of NHE-1 nor the inhibition of NHE-3. Thus, members of the Src family are volume-sensitive enzymes that may participate in the shrinkage-related reorganization of the cytoskeleton but are probably not responsible for the osmotic regulation of NHE.  (+info)

Regulation of endothelial cell myosin light chain kinase by Rho, cortactin, and p60(src). (3/335)

Inflammatory diseases of the lung are characterized by increases in vascular permeability and enhanced leukocyte infiltration, reflecting compromise of the endothelial cell (EC) barrier. We examined potential molecular mechanisms that underlie these alterations and assessed the effects of diperoxovanadate (DPV), a potent tyrosine kinase activator and phosphatase inhibitor, on EC contractile events. Confocal immunofluorescent microscopy confirmed dramatic increases in stress-fiber formation and colocalization of EC myosin light chain (MLC) kinase (MLCK) with the actin cytoskeleton, findings consistent with activation of the endothelial contractile apparatus. DPV produced significant time-dependent increases in MLC phosphorylation that were significantly attenuated but not abolished by EC MLCK inhibition with KT-5926. Pretreatment with the Rho GTPase-inhibitory C3 exotoxin completely abolished DPV-induced MLC phosphorylation, consistent with Rho-mediated MLC phosphatase inhibition and novel regulation of EC MLCK activity. Immunoprecipitation of EC MLCK after DPV challenge revealed dramatic time-dependent tyrosine phosphorylation of the kinase in association with increased MLCK activity and a stable association of MLCK with the p85 actin-binding protein cortactin and p60(src). Translocation of immunoreactive cortactin from the cytosol to the cytoskeleton was noted after DPV in concert with cortactin tyrosine phosphorylation. These studies indicate that DPV activates the endothelial contractile apparatus in a Rho GTPase-dependent fashion and suggests that p60(src)-induced tyrosine phosphorylation of MLCK and cortactin may be important features of contractile complex assembly.  (+info)

Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. (4/335)

NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.  (+info)

Tyrosine phosphorylation of cortactin associated with Syk accompanies thromboxane analogue-induced platelet shape change. (5/335)

Thromboxane A(2) (TxA(2)) is a potent vasoconstrictor and platelet agonist. Pharmacological studies have defined two classes of thromboxane receptors (TPs) in human platelets; sites that bind the agonist 1S-(1,2(5Z),3-(1E,3S),4)-7- 3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo-2.2. 1-heptan-2-yl-5-heptenoic acid (I-BOP) with high affinity support platelet shape change, whereas low affinity sites that bind irreversibly the antagonist GR 32191 transduce platelet aggregation. As the mechanisms of signal transduction involved in platelet aggregation begin to be elucidated, few results concern those involved in platelet shape change, which is independent of the engagement of GPIIb/IIIa. To elucidate the respective role of the two classes of pharmacological binding sites of TPs in shape change, platelets were incubated with I-BOP at low concentrations or stimulated by I-BOP at high concentrations after pretreatment with GR 32191 or activated with low concentrations of 8-epi-prostaglandin F(2)alpha. Under these three conditions, there is a rapid stimulation of protein tyrosine phosphorylation of the 80/85-kDa doublet identified as the cytoskeletal protein cortactin. Tyrosine phosphorylation of cortactin is kinetically correlated with the occurrence of shape change. These biochemical and morphological events are both inhibited by SQ 29548, a TP antagonist, indicating the specificity of the signal. Since tyrosine kinase Syk was activated early during platelet activation, we examined the possibility that cortactin is a potential substrate of Syk in TxA(2)-induced platelet shape change. p72 Syk phosphorylation and kinase activity took place during the period when platelets were changing shape upon low concentrations of I-BOP stimulation. Furthermore, cortactin was associated with Syk, and this association increases along with the level of phosphorylation. These data suggest a novel pathway for a G protein-coupled TxA(2) high affinity receptor to the protein-tyrosine kinase Syk, which is associated with cortactin in the very early steps of platelet activation.  (+info)

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation. (6/335)

Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (ECM). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) mu, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We confirmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates with cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.  (+info)

Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin. (7/335)

The structural characteristics of EMS1 (human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 gene is commonly amplified and overexpressed in several human cancers, which may alter their invasive or metastatic properties. An 80 to 85-kDa mobility shift of EMS1 correlates with an alteration in subcellular distribution and is likely to represent an important regulatory event. In HEK 293 cells, epidermal growth factor treatment or cell detachment induced this shift, and this was blocked by the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059. Furthermore, expression of a constitutively active form of MEK induced the shift, indicating that MEK activation was both sufficient and necessary for this modification. The epidermal growth factor-induced shift correlated with increased phosphorylation on serine and threonine residues of the same tryptic phosphopeptides detected under basal conditions. Deletion of the helical-proline-rich region of the protein blocked the mobility shift and EMS1 phosphorylation. In vitro kinase assays demonstrated that the extracellular signal-regulated kinases represent candidate kinases for this region, although other MEK-regulated enzymes must also participate. These data identify MEK as an important intermediate involved in EMS1 phosphorylation and highlight the helical-proline-rich region as a key regulatory domain.  (+info)

Synapse structure: glutamate receptors connected by the shanks. (8/335)

A family of proteins has been identified whose members, the Shanks, physically link two major receptor complexes at excitatory synapses - NMDA receptors and metabotropic glutamate receptors.  (+info)

*Cortactin

In humans, cortactin is encoded by the CTTN gene on chromosome 11. Cortactin is a thin, elongated monomer that consists of an ... Branches formed from cortactin-assisted nucleation sites are very stable; cortactin has been shown to inhibit debranching. Thus ... Ohoka Y, Takai Y (1998). "Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90". ... This basic structure is highly conserved among all species that express cortactin. Cortactin is activated via phosphorylation, ...

*CTTNBP2

Ohoka Y, Takai Y (1998). "Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90". ... Cortactin-binding protein 2 is a protein that in humans is encoded by the CTTNBP2 gene. This gene encodes a protein with six ... "Entrez Gene: CTTNBP2 cortactin binding protein 2". Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, ... "Identification of the human cortactin-binding protein-2 gene from the autism candidate region at 7q31". Genomics. 78 (1-2): 7- ...

*PTPN1

Stuible M, Dubé N, Tremblay ML (June 2008). "PTP1B regulates cortactin tyrosine phosphorylation by targeting Tyr446". J. Biol. ... beta-catenin and cortactin have also been described as PTP1B substrates. The first crystal structure of the PTP1B catalytic ...

*ARPC2

... has been shown to interact with Cortactin. GRCh38: Ensembl release 89: ENSG00000163466 - Ensembl, May 2017 GRCm38: ... "Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex". J ...

*ACTR3

Weed SA, Karginov AV, Schafer DA, Weaver AM, Kinley AW, Cooper JA, Parsons JT (Oct 2000). "Cortactin localization to sites of ... ACTR3 has been shown to interact with Cortactin. GRCh38: Ensembl release 89: ENSG00000115091 - Ensembl, May 2017 GRCm38: ... "Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex". ...

*DNM2

2003). "Dynamin2 and cortactin regulate actin assembly and filament organization". Curr. Biol. 12 (21): 1852-7. doi:10.1016/ ...

*FER (gene)

Kim, L; Wong T W (Sep 1998). "Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the ... Huang C, Liu J, Haudenschild CC, Zhan X (1998). "The role of tyrosine phosphorylation of cortactin in the locomotion of ... Kim L, Wong TW (1998). "Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the ... FER (gene) has been shown to interact with TMF1 and Cortactin. GRCh38: Ensembl release 89: ENSG00000151422 - Ensembl, May 2017 ...

*CDH2

Cheng, L; Yung, A; Covarrubias, M; Radice, GL (10 June 2011). "Cortactin is required for N-cadherin regulation of Kv1.5 channel ... KCNE2 and cortactin combined with disrupted actin cytoskeleton at the sarcolemma. In neural cells, at certain central nervous ...

*FGD1

Another interaction partner of FGD1 is cortactin, which is directly bound by the proline-rich domain of FGD1. As cortactin is ... The prolin-rich domain interacts with cortactin and actin-binding protein 1. FYVE-finger domains are conserved through ...

*WIPF1

Kinley AW, Weed SA, Weaver AM, Karginov AV, Bissonette E, Cooper JA, Parsons JT (Mar 2003). "Cortactin interacts with WIP in ... Kinley AW, Weed SA, Weaver AM, Karginov AV, Bissonette E, Cooper JA, Parsons JT (Mar 2003). "Cortactin interacts with WIP in ... WIPF1 has been shown to interact with Wiskott-Aldrich syndrome protein, Cortactin and NCK1. Majority of the mutations causing ...

*Coronin

Cai L, Makhov AM, Schafer DA, Bear JE (September 2008). "Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin ...

*NEDD9

... binds to and regulates acetylation of cortactin (CTTN) in an Aurora A kinase (AURKA)/HDAC6-dependent manner. The ... "NEDD9 regulates actin dynamics through cortactin deacetylation in an AURKA/HDAC6-dependent manner". Mol. Cancer Res. 12 (5): ...

*FYN

"Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho". J. Cell Biol. 162 (1): 99-111. doi: ...

*KCNA2

RHOA and Cortactin. Mutations in this gene have been associated with hereditary spastic paraplegia. Voltage-gated potassium ... "Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin". The Journal of ...

*CTNND1

... has been shown to interact with: Beta-catenin, CDH1, CDH2, Collagen, type XVII, alpha 1, Cortactin, FYN, MUC1, Nephrin, ... "Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho". J. Cell Biol. 162 (1): 99-111. doi: ...

*CORO1B

Studies related to this protein are as follows: Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches ... "Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches in lamellipodia". Cell. 134 (5): 828-42. doi: ...

*SHANK2

Du Y, Weed SA, Xiong WC, Marshall TD, Parsons JT (1998). "Identification of a novel cortactin SH3 domain-binding protein and ... Du Y, Weed SA, Xiong WC, Marshall TD, Parsons JT (October 1998). "Identification of a novel cortactin SH3 domain-binding ... This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a ... SHANK2 has been shown to interact with: ARHGEF7, Cortactin, DLG4, DLGAP1, and DNM2. GRCh38: Ensembl release 89: ENSG00000162105 ...

*TUBA1A

Kinnunen T, Kaksonen M, Saarinen J, Kalkkinen N, Peng HB, Rauvala H (April 1998). "Cortactin-Src kinase signaling pathway is ...

*NAA15

Paradis H, Islam T, Tucker S, Tao L, Koubi S, Gendron RL (15 June 2008). "Tubedown associates with cortactin and controls ...

*Rong Li

Activation of Arp2/3 complex-mediated actin polymerization by cortactin, in: Nature Cell Biology. Vol. 3, nº 3; 259-266. 1999, ...

*TUBB2A

1998). "Cortactin-Src kinase signaling pathway is involved in N-syndecan-dependent neurite outgrowth". J. Biol. Chem. 273 (17 ...

*ARHGAP8

Lua BL, Low BC (2004). "BPGAP1 interacts with cortactin and facilitates its translocation to cell periphery for enhanced cell ... Lua BL, Low BC (2005). "Filling the GAPs in cell dynamics control: BPGAP1 promotes cortactin translocation to the cell ...

*Tight junction protein 1

Katsube T, Takahisa M, Ueda R, Hashimoto N, Kobayashi M, Togashi S (Nov 1998). "Cortactin associates with the cell-cell ...

*MMP2

Clark ES, Whigham AS, Yarbrough WG, Weaver AM (May 2007). "Cortactin is an essential regulator of matrix metalloproteinase ...

*WASL (gene)

... has been shown to interact with: CDC42, Cortactin NCK1, Profilin 1, and RHOQ. GRCh38: Ensembl release 89: ...
Dynamic regulation of cell-cell adhesion by the coordinated formation and dissolution of E-cadherin-based adherens junctions is crucial for tissue homeostasis. The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1;also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. Two new S298-phosphorylation-dependent interactions were also identified, namely, that phosphorylation of cortactin decreases its interaction with beta-catenin and the actin-binding protein vinculin. In addition, binding of vinculin to beta-catenin, as well as linkage of vinculin to F-actin, are also significantly compromised upon ...
We present a molecular dissection of the functional domains of cortactin relevant for invadopodia formation and function. In addition, through the expression of cortactin forms mutated in the residues previously found to be phosphorylated in vitro, we suggest the involvement of different kinases in the control of the ECM degradation machinery through the regulation of cortactin phosphorylation.. The overexpression of mutant or deleted forms of cortactin that are unable to bind the Arp2/3 complex, induces a substantial decrease in the ability of the cells to form invadopodia and hence degrade the ECM. In addition, the SH3 domain of cortactin, known to bind a number of relevant proteins such as N-WASP and dynamin 2, is also essential for invadopodia formation and ECM degradation. This is at variance with a recent report suggesting that the cortactin N-terminus is not required for invadopodia formation (Webb et al., 2007). A possible explanation is that the study was based on constitutively active ...
Invasive carcinoma cells use specialized actin polymerization-driven protrusions called invadopodia to degrade and possibly invade through the extracellular matrix (ECM) during metastasis. Phosphorylation of the invadopodium protein cortactin is a master switch that activates invadopodium maturation and function. Cortactin was originally identified as a hyperphosphorylated protein in v-Src-transformed cells, but the kinase or kinases that are directly responsible for cortactin phosphorylation in invadopodia remain unknown. In this study, we provide evidence that the Abl-related nonreceptor tyrosine kinase Arg mediates epidermal growth factor (EGF)-induced cortactin phosphorylation, triggering actin polymerization in invadopodia, ECM degradation, and matrix proteolysis-dependent tumor cell invasion. Both Src and Arg localize to invadopodia and are required for EGF-induced actin polymerization. Notably, Arg overexpression in Src knockdown cells can partially rescue actin polymerization in ...
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) ...
Analyzing cortactin-deficient mice, we show for the first time that this actin-remodeling protein is required in endothelial cells, not in neutrophils, for optimal efficiency of neutrophil recruitment to inflamed tissue. Loss of cortactin caused an increase in rolling velocity and a decrease of neutrophil adhesion to the vessel wall. Thus, endothelial cortactin is required for slowing down rolling neutrophils and for firm adhesion to the vessel wall. Interestingly, cortactin was not required for the support of selectin-mediated rolling but for the slowing down of rolling mediated by β2-integrins and their ligands. In addition, formation of ICAM-1-containing clusters was disturbed, providing a possible explanation for the decreased numbers of neutrophils adhering to the vessel wall. Searching for a mechanism for this defect, we found that cortactin deficiency blocked the activation of RhoG triggered by ICAM-1 engagement, and CA-RhoG partially restored ICAM-1 clustering and neutrophil ...
The endocytic protein dynamin participates in the formation of actin-based membrane protrusions such as podosomes, pseudopodia, and invadopodia, which facilitate cancer cell migration, invasion, and metastasis. However, the role of dynamin in the formation of actin-based membrane protrusions at the leading edge of cancer cells is unclear. In this study, we demonstrate that the ubiquitously expressed dynamin 2 isoform facilitates cell migration by stabilizing F-actin bundles in filopodia of the lung cancer cell line H1299. Pharmacological inhibition of dynamin 2 decreased cell migration and filopodial formation. Furthermore, dynamin 2 and cortactin mostly colocalized along F-actin bundles in filopodia of serum-stimulated H1299 cells by immunofluorescent and immunoelectron microscopy. Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a loss of F-actin bundles. Expression of wild-type cortactin rescued the punctate-like ...
Invadopodia are actin-enriched cell protrusions that cancer cells use to degrade the extracellular matrix (ECM), which then allows for cancer cell invasion, and these processes require the binding of tyrosine-phosphorylated cortactin, an actin binding protein, with the Rho-family GTPase guanine nucleotide exchange factor (GEF) Vav2, which results in recruitment of Vav2 to invadopodia where Vav2 mediates invadopodial maturation and function through re-arrangement of the actin cytoskeleton, likely through activation of the Rac3 GTPase.
Cortactin兔单克隆抗体[EP1922Y](ab81208)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC, Flow Cyt, ICC/IF实验严格验证,被3篇文献引用并得到1个独立的用户反馈。
F-actin helps mitochondria divide by polymerizing on the organelles, Li et al. show.. The GTPase Drp1 forms spirals around mitochondria to cut the organelles in two. Studies suggest that actin also has a role in mitochondrial division and recruitment of Drp1. The mechanisms, however, remain unclear.. Li et al. found that F-actin polymerizes on the outer mitochondrial membrane in cultured cells but doesnt extend into the organelles. When the researchers spurred mitochondria to divide by putting them under stress, F-actin amassed on the organelles. However, latrunculin B, which prevents actin polymerization, curtailed this accumulation. Actin therefore gathers on mitochondria when they are ready to split.. The proteins cortactin and cofilin and the Arp2/3 complex-all of which spur actin to branch- also collect on mitochondria, Li et al. found. Depleting any of these factors led to extra-long mitochondria but didnt alter the rate of organelle fusion, suggesting that actin branching promotes ...
Sigma-Aldrich offers abstracts and full-text articles by [Jagadeesh Janjanam, Giri Kumar Chandaka, Sivareddy Kotla, Gadiparthi N Rao].
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Our research encompasses basic cell biology of tumor cell invasion, focusing on two tyrosine kinases, c-Src and Syk, with opposing roles in cancer metastasis. A major focus is invadopodia, the cell surface membrane protrusions formed during tumor cell invasion, and their role in invasion and metastasis. We use cortactin, a Src substrate, and MT1-MMP, an extracellular matrix-degrading, membrane protein, to identify and study the formation of invadopodia and acquisition of proteolytic activity. High resolution light and electron microscopy techniques are used to identify these structures and examine the membrane-associated signal transduction events that occur in conjunction with the formation of invadopodia. In vitro and in vivo assays are used to measure the consequent matrix adhesion, proteolysis and phagocytosis that are mediated by invadopodia. We also focus on determining the mechanism of breast cancer tumor suppression by the Syk tyrosine kinase. Utilizing mouse model systems, 3D culture ...
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Knockout Tested Rabbit recombinant monoclonal Cortactin antibody [EP1922Y]. Validated in WB, IP, IHC, Flow Cyt, ICC/IF and tested in Mouse, Rat, Human. Cited in 16 publication(s). Independently…
Esophageal cancer is an aggressive human malignancy with rising incidence in the developed world. The vascular endothelial growth factor VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. Upregulation of CTTN expression by VEGF-C enhanced the invasive propertis of esophageal squamous cell carcinoma (ESCC) in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR-326, thereby relieving the suppressive effect of miR-326 on CTTN expression. Clinically, expression of Dicer and miR-326 correlated with poor prognosis in esophageal cancer patients. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which ...
Ammer, A.G., and Weed, S.A. (2008). Cortactin branches out: roles in regulating protrusive actin dynamics. Cell Motil. Cytoskeleton 65: 687-707. PubMed Citation: 18615630 Arnaud, L., Ballif, B.A., Forster, E., and Cooper, J.A. (2003). Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development. Curr. Biol. 13: 9-17. 12526739 Baba, K., et al. (1999). The Drosophila Brutons tyrosine kinase (Btk) homolog is required for adult Survival and male genital formation. Mol. Cell. Biol. 19: 4405-4413. PubMed Citation: 10330180 Bei, Y., et al. (2002). SRC-1 and Wnt signaling act together to specify endoderm and to control cleavage orientation in early C. elegans embryos. Dev. Cell 3: 113-125. 12110172 Bershteyn, M., Atwood, S. X., Woo, W. M., Li, M. and Oro, A. E. (2010). MIM and cortactin antagonism regulates ciliogenesis and hedgehog signaling. Dev. Cell 19(2): 270-83. PubMed Citation: 20708589 Billuart, P., Winter, C. G., Maresh, A., Zhao, X. and Luo, L. (2001). Regulating axon ...
Immunocytochemistry for confocal microscopy. Sections were blocked in 20% normal donkey serum (NDS; Jackson ImmunoResearch, West Grove, PA) in 0.05 m PBS, pH 7.4, then incubated in various combinations of primary antibodies for cortactin, α-actinin, synaptophysin, and VGLUT1 in PBS containing 2% NDS overnight at room temperature. After several washes, sections were incubated in secondary antibodies (anti-rabbit Cy3 for cortactin, anti-mouse FITC for synaptophysin and VGLUT1). Alexa Fluor-488 conjugated to phalloidin (Molecular Probes, Eugene, OR) was used for visualization of F-actin (Allison et al., 1998). For visualization of cell processes, we used the lipophilic dye 3,3′-dioctadecyloxacarbocyanidine perchlorate (DiO; Molecular Probes), which infiltrates the plasma membrane, labeling even the finest neuronal processes (for details, see Burette et al., 2002). After several washes, sections were mounted on glass slides, coverslipped in Vectashield (Vector Laboratories, Burlingame, CA) and ...
TY - JOUR. T1 - CD44 regulates hepatocyte growth factor-mediated vascular integrity. T2 - Role of c-Met, Tiam1/Rac1, dynamin 2, and cortactin. AU - Singleton, Patrick A.. AU - Salgia, Ravi. AU - Moreno-Vinasco, Liliana. AU - Moitra, Jaideep. AU - Sammani, Saad. AU - Mirzapoiazova, Tamara. AU - Garcia, Joe GN. PY - 2007/10/19. Y1 - 2007/10/19. N2 - The preservation of vascular endothelial cell (EC) barrier integrity is critical to normal vessel homeostasis, with barrier dysfunction being a feature of inflammation, tumor angiogenesis, atherosclerosis, and acute lung injury. Therefore, agents that preserve or restore vascular integrity have important therapeutic implications. In this study, we explored the regulation of hepatocyte growth factor (HGF)-mediated enhancement of EC barrier function via CD44 isoforms. We observed that HGF promoted c-Met association with CD44v10 and recruitment of c-Met into caveolin-enriched microdomains (CEM) containing CD44s (standard form). Treatment of EC with ...
This protein protein interaction antibody pair set comes with two antibodies to detect the protein-protein interaction, one against the CASP3 protein, and the other against the CTTN protein for use in in situ Proximity Ligation Assay. See Publication Reference below. (DI0143) - Products - Abnova
Complete information for COTL1P1 gene (Pseudogene), Coactosin-Like F-Actin Binding Protein 1 Pseudogene 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Previous studies have suggested that N-syndecan regulates cell motility by binding to ECM-associated ligands like HB-GAM (for review see Rauvala et al., 2000). HB-GAM strongly promotes the haptotactic migration of forebrain cells, and the N-syndecan knockout cells fail completely to follow HB-GAM in vitro. The defective c-Src phosphorylation in the knockout cells is very likely associated with this failure. This interpretation is compatible with the finding that the cytosolic tail of N-syndecan binds a protein complex containing a PDZ domain protein calcium/CaM-dependent serine protein kinase (CASK), cortactin, and Fyn and Src kinases (Kinnunen et al., 1998b; Hsueh and Sheng, 1999; Lauri et al., 1999).. According to our findings, N-syndecan is important for the general migratory behavior of the forebrain cells. We demonstrate this by using EGFR-induced scatter behavior in forebrain cells as a test tool. Increasing EGFR activity in neural progenitor cells induces and promotes neural ...
Local actin filament formation powers the development of the signal-receiving arbor of neurons. In this study, Izadi et al. demonstrate that Cobl-like, which bears only a single WH2 domain, mediates dendritic branching by coordinating with the F-actin-binding protein Abp1 in a Ca2+/CaM-controlled manner to control actin dynamics. ...
Local actin filament formation powers the development of the signal-receiving arbor of neurons. In this study, Izadi et al. demonstrate that Cobl-like, which bears only a single WH2 domain, mediates dendritic branching by coordinating with the F-actin-binding protein Abp1 in a Ca2+/CaM-controlled manner to control actin dynamics. ...
From NCBI Gene:. This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]. From UniProt: ...
AFAP1L2 overexpression lysate, 0.1 mg. Transient overexpression lysate of actin filament associated protein 1-like 2 (AFAP1L2), transcript variant 2
Invadopodia facilitate cancer cell migration by breaking down the extracellular matrix that normally keeps cells in place. In previous research, Dr. Courtneidge discovered that Tks5 is crucial for invadopodia formation. The structural similarities between Tks5 and p47phox, which is part of the NADPH oxidase (Nox) system, led Dr. Courtneidge to consider the role reactive oxygen plays in invadopodia formation.. Using invadopodia-rich mouse fibrosarcoma cells, the Courtneidge laboratory tested a number of antioxidants and found both a marked reduction in invadopodia formation and invasive behavior. In addition, the team inhibited expression of Nox family enzymes with siRNA and had similar results, demonstrating that NADPH oxidases are involved in invadopodia formation. The scientists repeated these experiments with human melanoma, head and neck and breast cancer cell lines and also saw a marked reduction in invadopodia formation.. With the discovery of reactive oxygens role in invadopodia ...
The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transduction. Given the strong evidence that links signalling by certain families of RTKs to the progression of breast cancer, it is not surprising that the expression profile of key downstream signalling intermediates in this disease has also come under scrutiny, particularly because some exhibit transforming potential or amplify mitogenic signalling pathways when they are overexpressed. Reflecting the diverse cellular processes regulated by RTKs, it is now clear that altered expression of such signalling proteins in breast cancer may influence not only cellular proliferation (eg Grb2) but also the invasive properties of the cancer cells (eg EMS1/cortactin).
LSP1 Full-Length MS Protein Standard (NP_002330), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms.
Expression of CTTNBP2 (C7orf8, CORTBP2, KIAA1758, Orf4) in stomach 1 tissue. Antibody staining with HPA044654 and CAB009151 in immunohistochemistry.
Expression of CTTNBP2 (C7orf8, CORTBP2, KIAA1758, Orf4) in kidney tissue. Antibody staining with HPA044654 and CAB009151 in immunohistochemistry.
The pSUPER.retro (Oligoengine) RNA interference system was used to achieve stable expression of siRNAs. Oligonucleotides targeted to calpain 2 or PTP1B mRNA as well as a nonsilencing control were synthesized by Integrated DNA Technologies, annealed, and cloned into the pSUPER.retro.puro vector according to manufacturers instructions. Retroviral transfection was performed as described previously (Franco et al., 2004a). Wild-type MTLn3 cells were infected at 32°C for 6 h and allowed to recover in growth medium for 24 h before selection with 1 μg/ml puromycin for 4-5 d. Target sequences for calpain 2 in MTLn3 cells: control, 5′-TTCTCCGAACGTGTCACGT-3′; Capn2 si-A, 5′-AGGCCTATGCCAAGATCAA-3′; and Capn2 si-B, 5′-GAATGGCGATTTCTGCATC-3′. Target sequences for PTP1B in MTLn3 cells: PTP1B si-A, 5′-GCTGACACTGATCTCTGAA-3′; and PTP1Bsi-B, 5′-CAGGAGGAGCCTTGGTGTC-3′. Target sequences for human calpain 2 have been described previously (Su et al., 2006). Target sequences for cortactin: ...
Our results suggest that the inhibitory effect of adrenomedullin on the expression of HGF and COX-2 is mediated by CGRP receptors. DFT calculations of structures, (13)C NMR chemical shifts, and Raman RBM mode of simple models of small-diameter zigzag (4,0) carboxylated single-walled carbon nanotubes. At the end of the experiment, the corneas were processed for histological study. The patients with HK2 expression showed a worse prognosis compared to the HK2 negative cases, and patients who were negative in Bcl-2 and positive in HK2 represented the lowest survival rate. In this paper we have shown for first time that cationically modified pullulan has antiatherogenic potential and influences on lipid metabolism. Tissue was sampled generic cialis from the cranial part of the distal intermediate ridge of the tibia in the tarso-crural joint. Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric ...
View mouse Afap1l2 Chr19:56912361-57008228 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Z disc, actin filament binding, cardiac muscle fiber development, regulation of cell migration, regulation of cytoskeleton organization
... long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. LTP consolidation requires a period of sustained Arc synthesis driven by brain-derived neurotrophic factor (BDNF) signaling. Local infusion of the BDNF scavenger, TrkB-Fc, during LTP maintenance resulted in rapid reversion of LTP, inhibition of Arc synthesis and loss of enhanced Arc SUMO1ylation. Furthermore, coimmunoprecipitation analysis showed that SUMO1-ylated Arc forms a complex with the F-actin-binding protein drebrin A, a major regulator of cytoskeletal dynamics in dendritic spines. Although MPSL1 Arc also interacted with dynamin 2, calcium/calmodulindependentprotein kinase II-beta (CaMKII), and postsynaptic density protein-95 (PSD-95), these complexes lacked SUMOylated Arc. The results support a model in which newly synthesized Arc is SUMOylated and targeted ...
Invadosomes are actin-based structures involved in extracellular matrix degradation. Invadosomes is a term that includes podosomes and invadopodia, which decorate normal and tumour cells, respectively. They are mainly organised into dots or rosettes, and podosomes and invadopodia are often compared and contrasted. Various internal or external stimuli have been shown to induce their formation and/or activity. In this Commentary, we address the impact of the microenvironment and the role of matrix receptors on the formation, and dynamic and degradative activities of invadosomes. In particular, we highlight recent findings regarding the role of type I collagen fibrils in inducing the formation of a new linear organisation of invadosomes. We will also discuss invadosome plasticity more generally and emphasise its physio-pathological relevance. ...
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Cortactin, SH3 domain (IPR035716) | InterPro | EMBL-EBICortactin, SH3 domain (IPR035716) | InterPro | EMBL-EBI

Cortactin, SH3 domain (IPR035716). Short name: Cortactin_SH3 Overlapping homologous superfamilies *SH3-like domain superfamily ... Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich ... Cortactin was originally identified as a substrate of Src kinase [PMID: 2110361]. It is an actin regulatory protein that binds ... Roles of cortactin, an actin polymerization mediator, in cell endocytosis.. Acta Biochim. Biophys. Sin. (Shanghai) 38 95-103 ...
more infohttp://www.ebi.ac.uk/interpro/entry/IPR035716

Cortactin - WikipediaCortactin - Wikipedia

In humans, cortactin is encoded by the CTTN gene on chromosome 11. Cortactin is a thin, elongated monomer that consists of an ... Branches formed from cortactin-assisted nucleation sites are very stable; cortactin has been shown to inhibit debranching. Thus ... Ohoka Y, Takai Y (1998). "Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90". ... This basic structure is highly conserved among all species that express cortactin. Cortactin is activated via phosphorylation, ...
more infohttps://en.wikipedia.org/wiki/Cortactin

The Subcellular Organization of Cortactin in Hippocampus | Journal of NeuroscienceThe Subcellular Organization of Cortactin in Hippocampus | Journal of Neuroscience

Cortactin lies significantly farther from the PSD than α-actinin. B, Distances of gold particles coding for cortactin from the ... Cortactin in dendrites. We found that cortactin is also concentrated in dendritic shafts, although to a lesser degree than in ... However, cortactin has also been implicated in the morphogenesis of dendritic trees: δ-catenin can bind to cortactin (Weed et ... Spine morphology and cortactin. Recent experiments in cultured neurons (Hering and Sheng, 2003) suggest a role for cortactin in ...
more infohttp://www.jneurosci.org/content/24/46/10310

Anti-Cortactin antibody [4F11] KO Tested (ab33333) | AbcamAnti-Cortactin antibody [4F11] KO Tested (ab33333) | Abcam

Knockout Tested Mouse monoclonal Cortactin antibody [4F11]. Validated in WB, IP, ICC, ICC/IF and tested in Mouse, Rat, Chicken ... I can only see a single band at ˜ 100 kD that is not present in the total cortactin gel and cannot possibly be cortactin. I ... It may be possible that the ˜100 kDa band corresponds to the phosphorylated form of cortactin. Since the cortactin antibody ... No band was observed when CTTN (Cortactin) knockout samples were used. Wild-type and CTTN (Cortactin) knockout samples were ...
more infohttps://www.abcam.com/cortactin-antibody-4f11-ab33333.html

RCSB PDB - Protein Feature View 









 - Src substrate cortactin - Q60598 (SRC8 MOUSE)RCSB PDB - Protein Feature View - Src substrate cortactin - Q60598 (SRC8 MOUSE)

The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
more infohttp://www.rcsb.org/pdb/protein/Q60598

Recombinant Anti-Cortactin antibody [EP1922Y] KO Tested (ab81208) | AbcamRecombinant Anti-Cortactin antibody [EP1922Y] KO Tested (ab81208) | Abcam

Knockout Tested Rabbit recombinant monoclonal Cortactin antibody [EP1922Y]. Validated in WB, IP, IHC, Flow Cyt, ICC/IF and ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 488) (ab202648) *Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 647) (ab202650 ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 555) (ab215298) *Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 568) (ab215299 ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 594) (ab215300) *Anti-Cortactin antibody [EP1922Y] - BSA and Azide free ( ...
more infohttps://www.abcam.com/cortactin-antibody-ep1922y-ab81208.html

Cortactin Potentiates Bone Metastasis of Breast Cancer Cells | Cancer ResearchCortactin Potentiates Bone Metastasis of Breast Cancer Cells | Cancer Research

To examine the role of cortactin in tumor progression, wild-type cortactin and a tyrosine phosphorylation-deficient cortactin ... In vitro, cortactin binds to and cross-links F-actin into meshwork. The F-actin cross-linking activity of cortactin can be ... Overexpression of GFP-Cortactin Variants Did Not Affect the Growth of Breast Cancer Cells.. To study the effect of cortactin on ... Expression of GFP-cortactin proteins was further quantified by immunoblot analysis. As shown in Fig. 1 ⇓ , both GFP-cortactin ...
more infohttps://cancerres.aacrjournals.org/content/61/18/6906?ijkey=c1394870b8f5abf16b2180de8dfd4cab3df71cbc&keytype2=tf_ipsecsha

Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway. | Sigma-AldrichCortactin phosphorylation regulates cell invasion through a pH-dependent pathway. | Sigma-Aldrich

Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway.. [Marco A O Magalhaes, Daniel R Larson, ... Cortactin phosphorylation is a key step during invadopodia maturation, regulating Nck1 binding and cofilin activity. The ... We provide evidence that cortactin-cofilin binding is regulated by local pH changes at invadopodia that are mediated by the ... Furthermore, cortactin tyrosine phosphorylation mediates the recruitment of NHE1 to the invadopodium compartment, where it ...
more infohttps://www.sigmaaldrich.com/catalog/papers/22105349

Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90.  - PubMed - NCBIIsolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90. - PubMed - NCBI

... and have named the original cortactin as cortactin-A and the newly isolated forms as cortactin-B and -C. Cortactin-A, -B and -C ... Cortactin is a major phosphotyrosyl protein in pp60v-src-transformed chicken embryo cells. Cortactin binds to actin filament (F ... A deletion mutant analysis of cortactin-A and CBP90 revealed that the SH3 domain of cortactin-A was able to bind to the proline ... Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90.. Ohoka Y1, Takai Y. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/9813110?dopt=Abstract

Anti-Cortactin antibody [N1], N-term (GTX100253) | GeneTexAnti-Cortactin antibody [N1], N-term (GTX100253) | GeneTex

Rabbit Polyclonal Cortactin antibody [N1], N-term. Validated in WB, ICC/IF, IHC-P. Tested in Human, Mouse, Rat. Cited in 3 ... Green: Cortactin protein stained by Cortactin antibody [N1], N-term (GTX100253) diluted at 1:500.. Blue: Hoechst 33342 staining ... Cortactin antibody [N1], N-term detects Cortactin protein at cell membrane and cytoplasm by immunofluorescent analysis.. Sample ... There are currently no reviews for Cortactin antibody [N1], N-term (GTX100253). Be the first to share your experience with this ...
more infohttps://www.genetex.com/Product/Detail/Cortactin-antibody-N1-N-term/GTX100253

Cortactin Adopts a Globular... - Researchers - ANUCortactin Adopts a Globular... - Researchers - ANU

Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets. Citation. Cowieson, N, King, G, Cookson, D et al 2008 ... Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets, Journal of Biological Chemistry, vol. 283, no. 23, pp ...
more infohttps://researchers.anu.edu.au/publications/63056

CTTNBP2 (cortactin binding protein 2) - KOMP (Knockout Mouse Project)CTTNBP2 (cortactin binding protein 2) - KOMP (Knockout Mouse Project)

OMIM: CORTACTIN-BINDING PROTEIN 2; CTTNBP2*Gene Ontology: Cttnbp2 *Mouse Phenome DB: Cttnbp2 *UCSC: Chr.6:18,366,477-18,514,825 ... cortactin binding protein 2. Synonyms: 3010022N24Rik, 4732477G22Rik, 9130022E09Rik, Cortbp2, ORF4. Gene nomenclature, locus ...
more infohttps://www.komp.org/geneinfo.php?geneid=35347

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo | JEMCortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo | JEM

... or cortactin-specific siRNAs. 48 h later, cell lysates were immunoblotted for cortactin expression (top). Cortactin immunoblots ... human cortactin-6 (5′-ATGCAACTTATTGTATCTGAA-3′), murine cortactin-5 (5′-CAGAGATGTGCTAGTGGCTTA-3′), and murine cortactin-7 (5′- ... Cortactin is an actin-binding protein that promotes actin assembly (Ammer and Weed, 2008). Cortactin is ubiquitously expressed ... Generation of cortactin-deficient mice. (A) Domain organization of the cortactin protein and gene targeting strategy showing ...
more infohttp://jem.rupress.org/content/early/2011/07/21/jem.20101920

Cortactin is involved in transforming growth factor-beta1-induced epithelial-mesenchymal transition in AML-12 cells.Cortactin is involved in transforming growth factor-beta1-induced epithelial-mesenchymal transition in AML-12 cells.

However, the function of cortactin in epithelial-mesenchymal transition (EMT) remains elusive. Here we found that during ... Cortactin is an F-actin binding protein, regulating cell movement and adhesive junction assembly. ... Inhibition of the dephosphorylation of cortactin by sodium vanadate blocked TGF-beta1-induced EMT. Knockdown of cortactin by ... Cortactin / physiology*. Epithelial Cells / physiology. Histone Acetyltransferases / physiology. Humans. Kidney / cytology*. ...
more infohttp://www.biomedsearch.com/nih/Cortactin-involved-in-transforming-growth/19779649.html

PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration. | Sigma-AldrichPLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration. | Sigma-Aldrich

... cortactin phosphorylation, cortactin-WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC ... Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of ... PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration.. [Jagadeesh Janjanam, ... MCP1, a G protein-coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time- ...
more infohttps://www.sigmaaldrich.com/catalog/papers/26490115

miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression | Cancer ResearchmiR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression | Cancer Research

miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression. Chih-Chen Hong, Pai- ... Here we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin ( ... miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression ... miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression ...
more infohttp://cancerres.aacrjournals.org/content/early/2014/09/06/0008-5472.CAN-14-0524

Signaling pathways and structural domains required for phosphorylation of EMS1/cortactinSignaling pathways and structural domains required for phosphorylation of EMS1/cortactin

... human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 ... human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 ... The structural characteristics of EMS1 (human cortactin) suggest that it may link signaling events to reorganization of the ... Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin. Abstract. ...
more infohttps://www.garvan.org.au/research/publications/1255

Archive ouverte HAL - ATAT1/MEC-17 acetyltransferase and HDAC6 deacetylase control a balance of acetylation of alpha-tubulin...Archive ouverte HAL - ATAT1/MEC-17 acetyltransferase and HDAC6 deacetylase control a balance of acetylation of alpha-tubulin...

In addition, ATAT1 colocalizes with cortactin at the adherent surface of the cells and it is required for 2D migration and ... We previously found that in breast tumor MDA-MB-231 cells an increase of microtubule and cortactin acetylation upon inhibition ... We observed that ATAT1 tubulin acetyltransferase binds and regulates cortactin acetylation levels. ... In addition, ATAT1 colocalizes with cortactin at the adherent surface of the cells and it is required for 2D migration and ...
more infohttps://hal.archives-ouvertes.fr/hal-01712252

Endothelial cell cortactin coordinates ICAM-1 clustering and actin cyt by Jennifer Kowalski"Endothelial cell cortactin coordinates ICAM-1 clustering and actin cyt" by Jennifer Kowalski

In this study, we tested the hypotheses that the Src family kinase-cortactin pathway mediates association of ICAM-1 with the ... Our data suggest a model in which tyrosine phosphorylation of cortactin dynamically links ICAM-1 to the actin cytoskeleton, ... Cytoskeletal remodeling after ICAM-1 cross-linking was reduced by knockdown of cortactin by small interfering RNA, by ... We recently reported that Src kinase phosphorylation of endothelial cortactin regulates polymorphonuclear cell (PMN) ...
more infohttps://digitalcommons.butler.edu/facsch_papers/629/

News - Citation Spotlight: Vav2 GEF Binds Phosphorylated Cortactin for Activation of Rac3 in InvadopodiaNews - Citation Spotlight: Vav2 GEF Binds Phosphorylated Cortactin for Activation of Rac3 in Invadopodia

... and these processes require the binding of tyrosine-phosphorylated cortactin, an actin binding protein, with the Rho-family ... The authors found that two tyrosine-phosphorylated residues on cortactin (Y421 and Y466) bind the SH2 domain of Vav2, a guanine ... Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in ... Tyrosine-phosphorylated cortactin recruits Vav2 to invadopodia, which facilitates their maturation and subsequent invadopodia- ...
more infohttps://www.cytoskeleton.com/blog/vav2-gef-binds-phosphorylated-cortactin-for-activation-of-rac3-in-invadopodia/

News - Citation Spotlight: Vav2 GEF Binds Phosphorylated Cortactin for Activation of Rac3 in InvadopodiaNews - Citation Spotlight: Vav2 GEF Binds Phosphorylated Cortactin for Activation of Rac3 in Invadopodia

... and these processes require the binding of tyrosine-phosphorylated cortactin, an actin binding protein, with the Rho-family ... The authors found that two tyrosine-phosphorylated residues on cortactin (Y421 and Y466) bind the SH2 domain of Vav2, a guanine ... Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in ... Tyrosine-phosphorylated cortactin recruits Vav2 to invadopodia, which facilitates their maturation and subsequent invadopodia- ...
more infohttps://www.cytoskeleton.com/blog/cat/news/post/vav2-gef-binds-phosphorylated-cortactin-for-activation-of-rac3-in-invadopodia/

Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation |...Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation |...

To this end, cells were transfected with cortactinWT, cortactinY421,466,482F and cortactinY421D after cortactin knockdown (Fig ... cortactinS113D and cortactinWT after siRNA-mediated endogenous cortactin knockdown (Fig. 4C). Expression of cortactinS113A on a ... transient expression of cortactinΔNTA, cortactinW22A and cortactinΔSH3 substantially inhibited both, compared with cortactinWT- ... D) A375MM cells were transfected with cortactinWT, nonphosphorylatable cortactinS113A and pseudophosphorylated cortactinS113D. ...
more infohttp://jcs.biologists.org/content/121/3/369

Cortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylationCortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylation

Thus, cortactin, unexpectedly, is an important integration node for the dynamic regulation of protein complexes during ... The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we ... Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is ... In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of ...
more infohttps://epub.ub.uni-muenchen.de/46748/

Involvement of the Src-cortactin pathway in podosome formation and turnover during polarization of cultured osteoclasts |...Involvement of the Src-cortactin pathway in podosome formation and turnover during polarization of cultured osteoclasts |...

... cortactin (cor) and phosphorylated cortactin (cor pY421). (A) Cortactin/actin ratio image highlights cortactin association with ... In control cells, the average cortactin intensity calculated (±s.d.) was 61±27 (cortactin) and 432±132 (cortactin pY421). In ... cortactin and cortactin pY421. A comparison of actin and cortactin distributions revealed the complete overlap of the two ... the average cortactin intensity calculated (±s.d.) was 512±230 (cortactin) and 501±189 (cortactin pY421). Note the ten- or ...
more infohttp://jcs.biologists.org/content/119/23/4878

Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle...Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle...

Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle ... Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle ... Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle ... The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to ...
more infohttps://www.garvan.org.au/research/publications/10581
  • Wild-type (WT) and Cortactin knockout (KO) HeLa cell extracts (30 μg) were separated by 7.5% SDS-PAGE, and the membrane was blotted with Cortactin antibody [N N-term (GTX100253) diluted at 1:1000. (genetex.com)
  • An increase in cortactin expression in β5 integrin knockout eyecups was not observed in the region amplified using primer pairs for exons 2-6. (biotechniques.org)
  • This analysis utilized eyecups and neural retinas from wild-type, β5 integrin knockout mice as well as JNK2 knockout mice, which were originally used to test primer pairs, but were employed here as controls to determine whether the increase in cortactin expression observed in β5 integrin knockout eyecups was specific to that knockout. (biotechniques.org)
  • Additionally, knockdown of cortactin further promoted TGF-beta1-induced EMT in AML-12 cells, as determined by EMT markers and cell morphological changes. (biomedsearch.com)
  • Moreover, migration assay showed that cortactin knockdown promoted the migration of AML-12 cells, and also enhanced TGF-beta1-induced migration. (biomedsearch.com)
  • Cytoskeletal remodeling after ICAM-1 cross-linking was reduced by knockdown of cortactin by small interfering RNA, by expression of a cortactin mutant deficient in Src phosphorylation sites (cortactin3F), and by the Src kinase inhibitor PP2. (butler.edu)
  • In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. (garvan.org.au)
  • The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) downstream of cortactin were confirmed by the transient knockdown of each CDKI by specific small interfering RNAs, which led to partial rescue of cell cycle progression. (garvan.org.au)
  • Injection of MDA-MB-231 cells overexpressing GFP-cortactin into nude mice through cardiac ventricles caused bone osteolysis at a frequency ∼85% higher than that of cells expressing the vector alone, whereas injection of cells overexpressing the mutant deficient in tyrosine phosphorylation induced 74% fewer osteolytic metastases as compared with the control group. (aacrjournals.org)
  • In this study, we examined the metastatic ability of MDA-MB-231 breast cancer cells overexpressing wild-type cortactin and a cortactin mutant deficient in tyrosine phosphorylation. (aacrjournals.org)
  • All the isoforms were able to bind to F-actin, but only cortactin-A demonstrated an F-actin-crosslinking activity. (nih.gov)
  • In addition, cortactin-A was able to bind along the side of F-actin. (nih.gov)
  • CBP90 was able to bind to all the cortactin isoforms. (nih.gov)
  • The authors found that two tyrosine-phosphorylated residues on cortactin (Y421 and Y466) bind the SH2 domain of Vav2, a guanine nucleotide exchange factor (GEF) for Rho-family GTPases such as Rac. (cytoskeleton.com)
  • Using immunocytochemistry, we demonstrate here that cortactin (a protein implicated in actin filament nucleation, branching, and stabilization) is concentrated in hippocampal spines, where it colocalizes with F-actin. (jneurosci.org)
  • In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. (rupress.org)
  • Cortactin: Coordinating adhesion and the actin cytoskeleton at cellular protrusions. (ebi.ac.uk)
  • Cortactin is activated via phosphorylation, by tyrosine kinases or serine/threonine kinases, in response to extracellular signals like growth factors, adhesion sites, or pathogenic invasion of the epithelial layer. (wikipedia.org)
  • Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. (uni-muenchen.de)
  • Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is vitally dependent on vinculin-mediated protein interactions. (uni-muenchen.de)
  • Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain [ PMID: 15670811 ]. (ebi.ac.uk)
  • Previous studies have shown that cortactin is upregulated in breast, head and neck tumors, and phosphorylated on multiple sites by Src and ERK kinases. (linfield.edu)
  • Inhibition of the dephosphorylation of cortactin by sodium vanadate blocked TGF-beta1-induced EMT. (biomedsearch.com)
  • MCP1, a G protein-coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. (sigmaaldrich.com)
  • We previously found that in breast tumor MDA-MB-231 cells an increase of microtubule and cortactin acetylation upon inhibition of HDAC6 correlates with a decrease of matrix degradation and invasion in three-dimensional collagen I gel. (archives-ouvertes.fr)
  • Cortactin is very active in lamellipodia, protrusions of the cell membrane formed by actin polymerization and treadmilling that propel the cell along a surface as it migrates towards some target. (wikipedia.org)
  • Cortactin, unlike type I NPFs, can be found integrated within the lamellipodia. (biologists.org)
  • Cortactin was originally identified as a substrate of Src kinase [ PMID: 2110361 ]. (ebi.ac.uk)
  • Roles of cortactin, an actin polymerization mediator, in cell endocytosis. (ebi.ac.uk)
  • Studies have implicated cortactin in both clathrin-mediated endocytosis and clathrin-independent endocytosis. (wikipedia.org)
  • These data suggest that cortactin contributes to tumor metastasis by enhancing the interaction of tumor cells with endothelial cells and the invasion of tumor cells into bone tissues. (aacrjournals.org)
  • A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. (rupress.org)
  • Cortactin acts as a link between extracellular signals and lamellipodial "steering. (wikipedia.org)
  • In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1;also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. (uni-muenchen.de)
  • Interestingly, FaDu cells with reduced cortactin levels also exhibited a significant diminution in RhoA expression and activity, together with decreased expression of Skp2, a critical component of the SCF ubiquitin ligase that targets p27(Kip1) and p57(Kip2) for degradation. (garvan.org.au)
  • These findings identify a novel mechanism for regulation of proliferation in 11q13-amplified HNSCC cells, in which overexpressed cortactin acts via RhoA to decrease expression of Cip/Kip CDKIs, and highlight Skp2 as a downstream effector for RhoA in this process. (garvan.org.au)
  • This basic structure is highly conserved among all species that express cortactin. (wikipedia.org)
  • Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90. (nih.gov)
  • Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. (rupress.org)
  • Interestingly, the cells expressing either GFP-cortactin or the mutant did not show significant differences in growth in vitro or when injected m.f.p. in vivo . (aacrjournals.org)
  • In vitro , cortactin binds to and cross-links F-actin into meshwork. (aacrjournals.org)
  • We performed immunocytochemical experiments to find out whether cortactin is present in spiny neurons of the rat brain, and, if so, whether it concentrates in a location suited to transduce interactions between the synapse and the actin cytoskeleton. (jneurosci.org)
  • The protein sequence of cortactin features six and a half tandem copies of a unique 37-amino acid repeat domain and a SH3 3 domain at the COOH terminus. (aacrjournals.org)