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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
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.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
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.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
The prototypical and most well-studied member of the semaphorin family. Semaphorin-3A is an axon-repulsive guidance cue for migrating neurons in the developing nervous system. It has so far been found only in vertebrates, and binds to NEUROPILIN-1/plexin complex receptors on growth cones. Like other class 3 semaphorins, it is a secreted protein.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. (Alberts et al., Molecular Biology of the Cell, 2nd ed, p22)
A family of cytoskeletal proteins that play essential roles in CELL ADHESION at ADHERENS JUNCTIONS by linking CADHERINS to the ACTIN FILAMENTS of the CYTOSKELETON.
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.
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.
A condition with damage to the lining of the lower ESOPHAGUS resulting from chronic acid reflux (ESOPHAGITIS, REFLUX). Through the process of metaplasia, the squamous cells are replaced by a columnar epithelium with cells resembling those of the INTESTINE or the salmon-pink mucosa of the STOMACH. Barrett's columnar epithelium is a marker for severe reflux and precursor to ADENOCARCINOMA of the esophagus.
A written agreement for the transfer of patients and their medical records from one health care institution to another.
Tumors or cancer of the ESOPHAGUS.
A form of interference microscopy in which variations of the refracting index in the object are converted into variations of intensity in the image. This is achieved by the action of a phase plate.
Removal of all or part of the PROSTATE, often using a cystoscope and/or resectoscope passed through the URETHRA.
Disposal, processing, controlling, recycling, and reusing the solid, liquid, and gaseous wastes of plants, animals, humans, and other organisms. It includes control within a closed ecological system to maintain a habitable environment.
Steel wires, often threaded through the skin, soft tissues, and bone, used to fix broken bones. Kirschner wires or apparatus also includes the application of traction to the healing bones through the wires.
Wires of various dimensions and grades made of stainless steel or precious metal. They are used in orthodontic treatment.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
For-profit enterprise with relatively few to moderate number of employees and low to moderate volume of sales.
INFLAMMATION of the UDDER in cows.
The interchange of goods or commodities, especially on a large scale, between different countries or between populations within the same country. It includes trade (the buying, selling, or exchanging of commodities, whether wholesale or retail) and business (the purchase and sale of goods to make a profit). (From Random House Unabridged Dictionary, 2d ed, p411, p2005 & p283)
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Organic compounds that contain the -NCO radical.
The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
The nonstriated involuntary muscle tissue of blood vessels.
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.
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.
Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.
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.
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.
Proteins that are preferentially expressed or upregulated during FETAL DEVELOPMENT.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A family of low molecular weight proteins that bind ACTIN and control actin polymerization. They are found in eukaryotes and are ubiquitously expressed.
A malignant tumor of the bone which always arises in the medullary tissue, occurring more often in cylindrical bones. The tumor occurs usually before the age of 20, about twice as frequently in males as in females.
A plant species in the PIPERACEAE plant family. It is a common spice on foods and is used medicinally to increase gastrointestinal assimilation of other supplements and drugs. Piperine is a key component. Black pepper is picked unripe and heaped for a few days to ferment. White Pepper is the ripe fruit dehulled by maceration in water.
A ubiquitous hnRNP protein found in the CELL NUCLEUS and the CYTOPLASM. Translocations that result in the formation of fusion proteins containing parts of RNA-binding protein EWS may play a role in neoplastic processes such as EWING SARCOMA.
A member of the c-ets family of transcription factors that is preferentially expressed in cells of hematopoietic lineages and vascular endothelial cells. It was originally identified as a protein that provides a retroviral integration site for integration of FRIEND MURINE LEUKEMIA VIRUS.
Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.

CD28 ligation induces tyrosine phosphorylation of Pyk2 but not Fak in Jurkat T cells. (1/1828)

Protein tyrosine kinases are critical for the function of CD28 in T cells. We examined whether the tyrosine kinases Pyk2 and Fak (members of the focal adhesion kinase family) are involved in CD28 signaling. We found that ligating CD28 in Jurkat T cells rapidly increases the tyrosine phosphorylation of Pyk2 but not of Fak. Paxillin, a substrate for Pyk2 and Fak, was not tyrosine-phosphorylated after CD28 ligation. CD28-induced tyrosine phosphorylation of Pyk2 was markedly reduced in the absence of external Ca2+. Previous studies have shown that the T cell antigen receptor (TCR) induces tyrosine phosphorylation of Pyk2. In this report, the concurrent ligation of CD28 and TCR increased tyrosine phosphorylation of Pyk2; however, the extent of phosphorylation by both receptors was equivalent to the sum of that induced by each receptor alone. The Syk/Zap inhibitor piceatannol blocked CD28, and TCR induced tyrosine phosphorylation of Pyk2, suggesting that Syk/Zap is involved in Pyk2 phosphorylation. In contrast, the phosphatidylinositol 3-kinase inhibitor wortmannin blocked TCR- but not CD28-induced phosphorylation of Pyk2, suggesting that CD28 and TCR activate distinct pathways to induce tyrosine phosphorylation of Pyk2. Notably, depleting phorbol 12-myristate 13-acetate-sensitive protein kinase C did not block CD28- and CD3-induced tyrosine phosphorylation of Pyk2. These data provide evidence for the involvement of Pyk2 in the CD28 signaling cascade and suggest that neither Fak nor paxillin is involved in the signaling pathways of CD28.  (+info)

Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis. (2/1828)

Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G protein-coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)- RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation, and Galphai as well as JAK/STAT association to the receptor. 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. 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.  (+info)

Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. (3/1828)

The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins. On the other hand, IGF-I promotes the association of insulin receptor substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected cells. This impairment of cell migration is recovered by reintroduction of a catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity participates in the integrin deactivation process. Although SHP-2 regulates mitogen-activated protein kinase activity, the mitogen-activated protein kinase kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The role of SHP-2 as a general regulator of cell chemotaxis induced by other chemotactic agents and integrins is discussed.  (+info)

Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2. (4/1828)

The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2 binds to SHP substrate 1 (SHPS-1)/SIRP-1alpha, a transmembrane glycoprotein with adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887-6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223-13229). Therefore, we asked whether SHP2-SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl phosphorylation increased upon plating of murine fibroblasts onto specific extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1 tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced mitogen-activated protein kinase (MAPK) activation, and potentiation required functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we analyzed the responses of SHP-2 exon 3(-/-) and wild-type cell lines to being plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl phosphorylation of several focal adhesion proteins, MAPK activation, and the ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but were restored upon SHP-2 expression. Our data suggest a positive-feedback model in which, upon integrin engagement, basal levels of c-Src activity catalyze the tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces positive signals for downstream events such as MAPK activation and cell shape changes.  (+info)

Activation of the Cdc42-associated tyrosine kinase-2 (ACK-2) by cell adhesion via integrin beta1. (5/1828)

Activated Cdc42-associated kinase-2 (ACK-2) is a non-receptor tyrosine kinase that appears to be a highly specific target for the Rho-related GTP-binding protein Cdc42. In order to understand better how ACK-2 activity is regulated in cells, we have expressed epitope-tagged forms of this tyrosine kinase in COS-7 and NIH3T3 cells. We find that ACK-2 can be activated by cell adhesion in a Cdc42-dependent manner. However, unlike the focal adhesion kinase, which also is activated by cell adhesion, the activation of ACK-2 is F-actin-independent and does not require cell spreading. In addition, overexpression of ACK-2 in COS-7 cells did not result in the stimulation of extracellular signal-regulated kinase activity but rather activated the c-Jun kinase. Both anti-integrin beta1 antibody and RGD peptides inhibited the activation of ACK-2 by cell adhesion. In addition, ACK-2 was co-immunoprecipitated with integrin beta1. Overall, these findings suggest that ACK-2 interacts with integrin complexes and mediates cell adhesion signals in a Cdc42-dependent manner.  (+info)

Interactions between two cytoskeleton-associated tyrosine kinases: calcium-dependent tyrosine kinase and focal adhesion tyrosine kinase. (6/1828)

The calcium-dependent tyrosine kinase (CADTK), also known as Pyk2/RAFTK/CAKbeta/FAK2, is a cytoskeleton-associated tyrosine kinase. We compared CADTK regulation with that of the highly homologous focal adhesion tyrosine kinase (FAK). First, we generated site-specific CADTK mutants. Mutation of Tyr402 eliminated autophosphorylation and significantly decreased kinase activity. Mutation of Tyr881, a putative Src kinase phosphorylation site predicted to bind Grb2, had little effect on CADTK regulation. Src family tyrosine kinases resulted in CADTK tyrosine phosphorylation even when co-expressed with the Tyr402/Tyr881 double mutant, suggesting that Src/Fyn etc. phosphorylate additional tyrosine residues. Interestingly, CADTK tyrosine-phosphorylated FAK when both were transiently expressed, but FAK did not phosphorylate CADTK. Biochemical experiments confirmed direct CADTK phosphorylation of FAK. This phosphorylation utilized tyrosine residues other than Tyr397, Tyr925, or Tyr576/Tyr577, suggesting that new SH2-binding sites might be created by CADTK-dependent FAK phosphorylation. Last, expression of the CADTK carboxyl terminus (CRNK) abolished CADTK but not FAK autophosphorylation. In contrast, FAK carboxyl terminus overexpression inhibited both FAK and CADTK autophosphorylation, suggesting that a FAK-dependent cytoskeletal function may be necessary for CADTK activation. Thus, CADTK and FAK, which both bind to some, but not necessarily the same, cytoskeletal elements, may be involved in coordinate regulation of cytoskeletal structure and signaling.  (+info)

Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts. (7/1828)

In this article, we show that, in transfected COS-1 cells, protein tyrosine phosphatase (PTP)-PEST translocates to the membrane periphery following stimulation by the extracellular matrix protein fibronectin. When plated on fibronectin, PTP-PEST (-/-) fibroblasts display a strong defect in motility. 3 h after plating on fibronectin, the number and size of vinculin containing focal adhesions were greatly increased in the homozygous PTP-PEST mutant cells as compared with heterozygous cells. This phenomenon appears to be due in part to a constitutive increase in tyrosine phosphorylation of p130(CAS), a known PTP-PEST substrate, paxillin, which associates with PTP-PEST in vitro, and focal adhesion kinase (FAK). Another effect of this constitutive hyperphosphorylation, consistent with the focal adhesion regulation defect, is that (-/-) cells spread faster than the control cell line when plated on fibronectin. In the PTP-PEST (-/-) cells, an increase in affinity for the SH2 domains of Src and Crk towards p130(CAS) was also observed. In (-/-) cells, we found a significant increase in the level of tyrosine phosphorylation of PSTPIP, a cleavage furrow-associated protein that interacts physically with all PEST family members. An effect of PSTPIP hyperphosphorylation appears to be that some cells remain attached at the site of the cleavage furrow for an extended period of time. In conclusion, our data suggest PTP-PEST plays a dual role in cell cytoskeleton organization, by promoting the turnover of focal adhesions required for cell migration, and by directly or indirectly regulating the proline, serine, threonine phosphatase interacting protein (PSTPIP) tyrosine phosphorylation level which may be involved in regulating cleavage furrow formation or disassembly during normal cell division.  (+info)

Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal. (8/1828)

We previously demonstrated contrasting roles for integrin alpha subunits and their cytoplasmic domains in controlling cell cycle withdrawal and the onset of terminal differentiation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A.F. Horwitz. 1996. J. Cell Biol. 133:169-184). Ectopic expression of the integrin alpha5 or alpha6A subunit in primary quail myoblasts either decreases or enhances the probability of cell cycle withdrawal, respectively. In this study, we addressed the mechanisms by which changes in integrin alpha subunit ratios regulate this decision. Ectopic expression of truncated alpha5 or alpha6A indicate that the alpha5 cytoplasmic domain is permissive for the proliferative pathway whereas the COOH-terminal 11 amino acids of alpha6A cytoplasmic domain inhibit proliferation and promote differentiation. The alpha5 and alpha6A cytoplasmic domains do not appear to initiate these signals directly, but instead regulate beta1 signaling. Ectopically expressed IL2R-alpha5 or IL2R-alpha6A have no detectable effect on the myoblast phenotype. However, ectopic expression of the beta1A integrin subunit or IL2R-beta1A, autonomously inhibits differentiation and maintains a proliferative state. Perturbing alpha5 or alpha6A ratios also significantly affects activation of beta1 integrin signaling pathways. Ectopic alpha5 expression enhances expression and activation of paxillin as well as mitogen-activated protein (MAP) kinase with little effect on focal adhesion kinase (FAK). In contrast, ectopic alpha6A expression suppresses FAK and MAP kinase activation with a lesser effect on paxillin. Ectopic expression of wild-type and mutant forms of FAK, paxillin, and MAP/erk kinase (MEK) confirm these correlations. These data demonstrate that (a) proliferative signaling (i.e., inhibition of cell cycle withdrawal and the onset of terminal differentiation) occurs through the beta1A subunit and is modulated by the alpha subunit cytoplasmic domains; (b) perturbing alpha subunit ratios alters paxillin expression and phosphorylation and FAK and MAP kinase activation; (c) quantitative changes in the level of adhesive signaling through integrins and focal adhesion components regulate the decision of myoblasts to withdraw from the cell cycle, in part via MAP kinase.  (+info)

Background: Deletion in liver cancer gene (DLC1) and phosphorylated focal adhesion kinase (p-FAK) have recently been reported as metastasis-related genes. However, the roles and prognostic values of their expression in epithelial ovarian carcinomas (EOCs) remain unclear. Methods: The expression and prognostic value of DLC1 and p-FAK Y397 in EOC were evaluated by immunohistochemistry and multivariate analysis. Results: Low expression of DLC1 and high expression of p-FAK Y397 were found in the 76 cases of EOC. The expression of DLC1 and p-FAK Y397 were negatively correlated. Multivariate analysis showed that the combination of them was an independent prognostic marker of EOC (P = 0.0319). Conclusions: DLC1 and pFAK Y397 had an association with the clinicopathologic characteristics of EOC. Expression of neither of these genes was a prognostic factor alone, but the combination revealed a significant prognostic value in the 60 cases of advanced stage EOC.
A decreased apoptotic response toward noxious stress is an issuing characteristic of the aging phenotype. Hydrogen peroxide or staurosporine induced apoptosis readily in young cells but not in senescent cells. We showed that focal adhesion kinase (FAK) expression and its phosphorylation at Tyr397, autophosphorylation site for focal adhesion formation, and Tyr577, Src-dependent phosphorylation site, were both increased in senescent cells. Moreover, FAK was inactivated proteolytically by apoptotic stimuli in young cells, but not in senescent cells. In addition, senescent cells whose FAK expression was downregulated by siRNA showed the increased level of apoptosis by staurosporine treatment via caspase-3 activation but not by hydrogen peroxide treatment. Interestingly dephosphorylation at Tyr577 of FAK by PP2 treatment, Src-family kinase inhibitor, induced the apoptosis by staurosporine in senescent cells but dephosphorylation at Tyr397 by downregulation of caveolin-1 was not affected. These data ...
For epithelial cancer cells to invade and metastasize, they are required to remodel their cell-matrix adhesions, detach, migrate, and adhere at distant sites within the body. A number of signaling pathways are involved in this process and here we addressed the role of Src and FAK in adhesion remodeling in colon cancer epithelial cells. Tyrosine phosphorylation of FAK is required for the ability of KM12C cells to turnover their adhesions, which is associated with cell motility. This is in accordance with work on viral Src where the Src-induced phosphorylation of FAK is linked with proteolytic cleavage of FAK by calpain required for both cell transformation and focal adhesion turnover and migration (41, 42) . Specifically, expression of FAK 407-925F prevented focal adhesion turnover and cell migration in fibroblasts (43) and a similar pathway may be initiated upon expression of this interfering mutant in KM12C cells where analysis of adhesion dynamics in real time revealed a defect in the ability ...
Materials and constructs. Sequence targeting the human PLCγ1 mRNA was subcloned into pSuper and pSuperior vectors (ref. 17; Supplementary Fig. S1B). Control vectors (pSuper 3Mut and pSuperior 3Mut) contain a three-point mutated sequence unable to target the human PLCγ1 mRNA (Supplementary Fig. S1B). Palm-HA-PLCγ1 was kindly provided by Dr. E. Bonvini (MacroGenics, Inc.). Antibodies were as follows: phosphorylated PLCγ1 (Tyr783), PLCγ1, phosphorylated epidermal growth factor receptor (EGFR; Tyr992), EGFR, phosphorylated AKT (Ser473), AKT, phosphorylated extracellular signal-regulated kinases (ERK), and ERKs from Cell Signaling; phosphorylated focal adhesion kinase (FAK; Tyr397) from BioSource; Rac1, FAK, paxillin, and glyceraldehyde-3-phosphate dehydrogenase from Santa Cruz Biotechnology; phosphorylated Tyr (4G10) from UBI; and CD44 from Novocastra Laboratories Ltd.. Cell culture, transfection, and RNA interference. MDA-MB-231 and U87 cells were grown in DMEM; MDA-MB-435 and TSA were grown ...
PND-1186, also known as SR-2156 and VS-4718, is a potent FAK inhibitor with a 50% inhibitory concentration (IC50) of 1.5 nM in vitro. PND-1186 has an IC50 of ~100 nM in breast carcinoma cells. Notably, 1.0 µM PND-1186 (|5-fold above IC50) had limited effects on cell proliferation. However, under non-adherent conditions as spheroids and as colonies in soft agar, 0.1 µM PND-1186 blocked FAK and p130Cas tyrosine phosphorylation, promoted caspase-3 activation, and triggered cell apoptosis. PND-1186 inhibited 4T1 breast carcinoma subcutaneous tumor growth correlated with elevated tumor cell apoptosis and caspase 3 activation.
OxLDL drives NF-κB activation and VCAM-1 expression through integrin-α5β1-dependent FAK signaling; however, the mechanisms regulating FAK-dependent NF-κB signaling have remained elusive (Yurdagul et al., 2014). Here, we define a new signaling pathway involving FAK-dependent activation of the RSK pathway to promote NF-κB activation through its classic upstream mediator IKKβ. Although both RSK and NF-κB activation are known to be redox sensitive, we show that preventing integrin signaling or FAK activation does not significantly affect oxLDL-induced ROS levels, suggesting that FAK-dependent activation of the RSK-IKKβ-NK-κB pathway operates independently from oxidative stress (Abe et al., 2000; Kabe et al., 2005). Instead, oxLDL drives FAK-dependent ERK activation that results in RSK-dependent signaling to IKKβ and NF-κB. We further demonstrate elevated FAK activation in the endothelium overlying both mouse and human atherosclerotic plaques, and show that transgenic mice containing an ...
Focal adhesion kinase (FAK) is an important mediator of extracellular matrix-integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in nonmalignant, nonmotile epithelial cells is not well understood. We previously showed that hepatocytes demonstrated activated FAK near stiff collagen tracts in fibrotic livers. In this study, we examined the role of liver epithelial FAK by inducing fibrotic liver disease in mice with liver epithelial FAK deficiency. We found that mice that lacked FAK in liver epithelial cells developed more severe liver injury and worse fibrosis as compared with controls. Increased fibrosis in liver epithelial FAK-deficient mice was linked to the activation of several profibrotic pathways, including the hedgehog/smoothened pathway. FAK-deficient ...
A new study published in the Journal of Biology describes how a protein that promotes cell growth allows cells to metastasise and spread through the bloodstream. Cancer cells are confined to the tissue in which they arise unless they can find a way into the bloodstream. The growth factor VEGF enables cells to do this by loosening connections between endothelial cells that form the lining of blood vessel walls.. VEGF triggers the phosphorylation of a protein called VEC, which serves to fasten endothelial cells together. As a result of this process, complexes that contain VEC fall apart, opening gaps between endothelial cells. Focal adhesion kinase (FAK), which accumulates at cell-to-cell junctions in the presence of VEGF, may play a role in VEC phosphorylation.. Scientists from the UC San Diego Moores Cancer Center gave a FAK inhibitor to a group of mice with fast-spreading breast cancer and a group with ovarian tumors in an attempt to pinpoint the function of the protein. It was discovered that ...
Supplementary MaterialsS1 Fig: Microscopy analysis of rS6p phosphorylation in macrophages infected by (L. (unpaired T-test).(EPS) ppat.1006088.s002.eps (1.8M) GUID:?807D17F7-CE76-4E3A-AF38-D551A18C5723 S3 Fig: Microscopy analysis of infected BMMs with aberrant nuclear morphology. (a-b) […]. ...
Cytosolic calcium ion concentrations ([Ca2+]we) were measured in rat neocortical synaptosomes using fura-2 and depolarization of synaptosomal membranes was induced by K+ (30?mM). existence from the P/Q-type Ca2+ route blocker […]. ...
The findings are published in this weeks online issue of The Journal of Cell Biology. Blood vessels are tightly lined with endothelial cells, which form a permeability barrier to circulating cells and molecules. Our studies show that pharmacological or genetic inhibition of the endothelial protein focal adhesion kinase, or FAK, prevents tumor spread by enhancing the vessel barrier function. The researchers found that selective FAK inhibition within endothelial cells prevented spontaneous tumor metastasis without alterations in tumor size. Schlaepfer, with colleagues at the UC San Diego Moores Cancer Center, is exploring whether inhibiting targets like FAK, which has important regulatory functions in both tumor cells and blood vessels, might provide a dual mechanism for preventing both cancer growth and spread. Using mouse models of breast, ovarian and melanoma tumors, first author Christine Jean, PhD, showed that FAK activity was elevated in the blood vessels surrounding tumors, compared to ...
Crystal Structures of the FAK Kinase in Complex with TAE226 and Related Bis-Anilino Pyrimidine Inhibitors Reveal a Helical DFG Conformation. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
A multiple-functionalized targeting delivery system was prepared by self-assembly for efficient delivery of Cas9/sgRNA plasmids to targeted tumor cell nuclei. The Cas9/sgRNA plasmids were compacted by protamine in the presence of calcium ions to form nanosized cores, which were further decorated by peptide and aptamer conjugated alginate derivatives. With the help of the nuclear location signal peptide and AS1411 aptamer with specific affinity for nucleolin in the tumor cell membrane and nuclei, the delivery vector can specifically deliver the plasmid to the nuclei of tumorous cells for knocking out the protein tyrosine kinase 2 (PTK2) gene to down-regulate focal adhesion kinase (FAK). The tumor cell apoptosis induced by genome editing is mitochondrial-dependent. In addition, FAK knockout results in negative regulation on the PI3K/AKT signaling pathway. Meanwhile, favorable modulation on various proteins involved in tumor progression can be realized by genome editing. The enhanced E-cadherin and ...
FAK (phospho Tyr397) antibody (PTK2 protein tyrosine kinase 2) for ICC/IF, IHC-Fr, WB. Anti-FAK (phospho Tyr397) pAb (GTX24803) is tested in Human, Mouse, Xenopus laevis samples. 100% Ab-Assurance.
FAK (phospho Tyr861) antibody (PTK2 protein tyrosine kinase 2) for WB. Anti-FAK (phospho Tyr861) pAb (GTX50133) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
引用Abcams Anti-FAK抗体[EP695Y] (ab40794)的参考文献列表。为您列举引用本产品的发表文章,并提供信息包括论文文献数据库中的检索编号以便您搜寻文章
Overall, our data suggest an important role for the FERM domain in the activation of FAK and indicate that integrin signalling plays a limited role in the in vivo activation of FAK at least during the early stages of development.
FAK兔多克隆抗体(ab55335)可与小鼠, 大鼠, 人样本反应并经WB, ELISA, IHC实验严格验证,被1篇文献引用。所有产品均提供质保服务,中国75%以上现货。
Dr. Lim said this research has the potential to greatly impact patient care. Since there is currently a lack of therapeutics for the treatment of small vessel occlusions, which commonly occur in diabetic patients, this research could provide a new therapy for those patients, Dr. Lim said. Oral FAK inhibitors are currently being tested in human clinical trials as a cancer therapy; they might also prove helpful in treating these vascular complications ...
Rabbit recombinant monoclonal FAK (phospho Y397) antibody [EP2160Y] validated for WB, ICC/IF and tested in Human, Mouse and Rat. Referenced in 6 publications…
Mouse monoclonal FAK antibody [63D5] validated for WB, IP, ELISA, Flow Cyt, ChIP and tested in Human, Mouse and Rat. Referenced in 4 publications. Immunogen…
Results: Our data have shown that manipulating of the expression of CD24 in the tested cancer model cell lines resulted in a significant change in the expression level of Cten which in turn caused changes in the expression levels of ILK and FAK. Noticeable modifications to cell migration, invasion, proliferation, and colony-forming rate (all p,0.05) following CD24 manipulation have also been detected, indicating that the up-regulation of Cten, ILK and FAK expression by CD24 may reveal the mechanism via which cell functions are regulated. The up-regulation of Cten expression by CD24 was found to be due to protein stabilisation as confirmed by qPCR and CHX assy. CD24 was observed to activate AKT at Serine 473 (Ser473), rather than at the Threonine 308 (Thr308) residue, and potentially collaborate with PI3 kinase to induce the full activation of AKT. The inhibition of EGFR using a specific EGFR inhibitor, PD135053, and the stimulation of EGF using recombinant EGF in cell lines that did not harbour ...
Mouse Monoclonal Anti-FAK Antibody (4A9D6). Focal Adhesion Marker. Validated: WB, ELISA. Tested Reactivity: Human. 100% Guaranteed.
Pages 385-388 KORKMAZ AGAOGLU O, CINAR KUL B, AKYUZ B, ELMAZ O, OZCELIK METIN M, SAATCI M, ERTUGRUL O DOI : 10.9775/kvfd.2011.5456 ...
The audience comments from Dr. Harveys Part 1 webinar on coping with COVID-19 revealed an amazing but not surprising richness and resiliency. This follow-up webinar will have a small presentation followed by a Q & A exchange about what the COVID-19 has to offer us beyond hardship and fear. Harvey will elicit insights from the audience about how this terrifying, surrealistic pandemic can catalyze personal psychological growth; how we can come through the COVID-19 crisis far more united than divided, far more energized than depleted, and far more loving, far more enlightened. ...
Background Focal adhesion Kinase (FAK) is a nonreceptor proteins tyrosine kinase that is overexpressed in tumors and plays a significant role in tumor survival and PD318088 metastasis. in matched main tumors by Spearman correlation analysis. In addition a strong positive correlation was observed between high FAK expression and shorter overall survival and progression free survival in patients with metastatic tumors. Conclusions The data demonstrate a high potential for FAK as a therapeutic target especially in triple-negative breast cancer patients with high FAK expression. Rabbit Polyclonal to BLNK (phospho-Tyr84). (not shown). Thus these data suggest that targeting FAK in triple-negative breast cancer patients is usually a promising approach. It is important to note that FAK has many binding partners and integrates multiple oncogenic survival pathways and sequesters tumor-suppressor pathways [1 22 Therefore future therapeutics should involve multiple targets cross-linked with FAK survival ...
The objectives of this research were to better characterize the protein signaling complexes that form in response to spermatozoa binding to the bovine oocyte vitelline membrane and to elucidate their potential involvement in oocyte activation. Integrins located on the vitelline membrane of bovine oocytes have been implicated in mediating the sperm-oocyte interaction. Anti-integrin function blocking antibodies and immunofluorescence were utilized in order to reveal that the αV and β1 integrin subunits are essential for fertilization in the bovine and could form the integrin heterodimer involved in the sperm-oocyte interaction. Focal adhesion kinase is localized to focal adhesions and is a key component of signal transduction pathways mediated by integrins. The presence of focal adhesion kinase in bovine oocytes was verified by real-time polymerase chain reaction and immunoprecipitation and the localization of focal adhesion kinase at the site of sperm binding to the oocyte plasma membrane was verified
RhoJ is a RhoGTPase expressed in endothelial cells and tumour cells which regulates cell motility, invasion, endothelial tube formation and focal adhesion numbers. This study aimed to further delineate the molecular function of RhoJ. Using timelapse microscopy RhoJ was found to regulate focal adhesion disassembly; siRNA-mediated knockdown of RhoJ increased focal adhesion disassembly time, while expression of an active mutant (daRhoJ) decreased it. Further, daRhoJ co-precipitated with the GIT-PIX complex, a regulator of focal adhesion disassembly. An interaction between daRhoJ and GIT1 was confirmed using yeast-2-hybrid, which depended on the Spa homology domain of GIT1. GIT1, GIT2, β-PIX and RhoJ all co-localised in focal adhesions and depended on each other for their recruitment to focal adhesions. Functionally, the GIT-PIX complex regulated endothelial tube formation, with knockdown of GIT1/2 or β-PIX phenocopying RhoJ knockdown. RhoJ knockout mice showed reduced tumour growth and diminished ...
FAK (focal Adhesion Kinase or PTK2) is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility. FAK is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. FAK is a member of the FAK subfamily of protein tyrosine kinases that included PYK2 but lacks significant sequence similarity to kinases from other subfamilies. With the exception of certain types of blood cells, most cells express FAK. FAK tyrosine kinase activity can be activated, which plays a key important early step in cell migration.
TY - JOUR. T1 - Stretch-induced cell proliferation is mediated by FAK-MAPK pathway. AU - Wang, Ju Guang. AU - Miyazu, Motoi. AU - Xiang, Peng. AU - Li, Shu Nong. AU - Sokabe, Masahiro. AU - Naruse, Keiji. PY - 2005/4/29. Y1 - 2005/4/29. N2 - Previously we reported that a uni-axial cyclic stretch treatment of rat 3Y1 fibroblasts induced focal adhesion kinase (FAK) tyrosine phosphorylation followed by mitogen-activated protein kinase (MAPK) activation (Wang et al., 2001) [Wang, J.G., Miyazu, M., Matsushita, E., Sokabe, M., Naruse, K., 2001. Uni-axial cyclic stretch induces focal adhesion kinase (FAK) tyrosine phosphorylation followed by mitogen-activated protein kinase (MAPK) activation. Biochem. Biophys. Res. Comm. 288, 356-361]. In the present study, we investigated whether stretch-induced MAPK activation leads to proliferation of fibroblasts. 3Y1 fibroblasts were subjected to a uni-axial cyclic stretch treatment (1 Hz, 120% in length) and the bromodeoxyuridine (BrdU) incorporation was measured ...
Fak is rapidly activated and triggers the assembly of a multicomponent signaling complex that has been considered to occupy a central position in the transduction and coordination of the earlier responses of cardiac myocytes to mechanical stress. In the present study, we showed comprehensive data on Fak tyrosine phosphorylation, subcellular distribution, and interaction with C-terminal region of myosin heavy chain, providing insight on the mechanism of its activation by mechanical forces in cardiac myocytes.. By using phosphospecific antibodies against tyrosine residues of Fak and Src, we extended previous demonstration of Fak/Src signaling complex activation by mechanical stress, to show the load-induced phosphorylation of specific Fak tyrosine residues Tyr397, 576/7, 861, and 925 in the rat myocardium. These results agree with a proposed model for Fak activation triggered by autophosphorylation at Tyr397 followed by the engagement of Src, which phosphorylates additional Fak tyrosine ...
Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7s NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Altogether, our findings provide critical ...
Immunofluorescence studies with protein phosphatase-1 (PP1) isoforms-specific antibodies detected PP1δ, but not α or γ1, at focal adhesions. PP1δ also co-immunoprecipitated with the focal adhesion kinase (FAK) and the αv-integrin. In the present study glutathione S-transferase (GST)-PP1δ pulled-down FAK from fibroblasts extract and the interaction domain localized between residues 159 and 295 of δ. The association was confirmed by the ability to GST-FAK-related non-kinase (FRNK) to pull-down PP1δ from fibroblasts extract. GST-FRNK also pulled-down purified muscle PP1 catalytic subunit, thus indicating direct interaction between FAK and PP1. FAK displays consensus sequences for phosphorylation by cell division cycle kinase-2-cyclin B, and might be a PP1 substrate. In fact, FAK immunoprecipitated from metabolically-labelled mitotic HeLa cells without tyrosine phosphatase inhibitors was phosphorylated on Ser only and was dephosphorylated in vitro by purified muscle PP1, with loss of ...
Cell motility is stimulated by extracellular stimuli and initiated by intracellular signaling proteins that localize to sites of cell contact with the extracellular matrix termed focal contacts. Focal adhesion kinase (FAK) is an intracellular protein-tyrosine kinase (PTK) that acts to regulate the c …
Fingerprint Dive into the research topics of The role of focal adhesion kinase binding in the regulation of tyrosine phosphorylation of paxillin. Together they form a unique fingerprint. ...
PTK2; FAK; FAK1; Focal adhesion kinase 1; FADK 1; Focal adhesion kinase-related nonkinase; FRNK; Protein phosphatase 1 regulatory subunit 71; PPP1R71; Protein-tyrosine kinase 2; p125FAK; pp125FAK ...
GTPase regulator associated with the focal adhesion kinase (GRAF), a putative tumor suppressor gene, is found inactivated in hematopoietic malignancies by either genetic or epigenetic abnormalities. However, the expression level of GRAF gene has not yet been studied in leukemia. The aim of this study was to investigate the expression level of GRAF gene in those patients with myeloid malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML). The expression levels of GRAF transcript were determined in 94 patients using real-time quantitative PCR (RQ-PCR). Clinical and laboratory data of these patients were collected and analyzed. The significantly decreased level of GRAF transcript was observed in three myeloid malignancies compared to controls. Within AML, there was no difference in the level of GRAF transcript among different FAB subtypes (P | 0.05). Difference was not observed in the amount of GRAF mRNA between CML at chronic phase and
Chatterji T, Varkaris AS, Parikh NU, Song JH, Cheng CJ, Schweppe RE, Alexander S, Davis JW, Troncoso P, Friedl P, Kuang J, Lin SH, Gallick GE. Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells. Oncotarget. 2015 Apr 30; 6(12):10175-94 ...
This study is a Phase I dose escalation study in subjects with solid tumors. Part 1 will identify the maximum tolerated dose (MTD) using a dose-escalation procedure. Following identification of the MTD, enrollment into Parts 2, 3, 4, and 5 may be concurrent. Part 2 will explore further the safety, PK, tolerability, and anti-tumor activity of GSK2256098 in subjects with tumors known to overexpress focal adhesion kinase (FAK). Part 3 will characterize the range of biologically effective doses by assessing pharmacodynamic (PD) markers in hair, skin and tumor tissue at doses that will not go lower than 80 mg or above the MTD dose levels tested during the Phase 1 dose escalation. Part 4 will explore further the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM). The primary objective of this study is to determine the safety, tolerability, and MTD of GSK2256098. Secondary objectives are to characterize the pharmacokinetics (PK) of ...
Autor: Volberg, T. et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2001-06; Keywords: Animals; Cell Adhesion Molecules/metabolism; Cell Line; Cell-Matrix Junctions/drug effects/enzymology/*metabolism; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions/drug effects/enzymology/metabolism; Gene Deletion; Mice; Microfilament Proteins/metabolism; Microscopy, Fluorescence; Phosphorylation/drug effects; Phosphotyrosine/metabolism; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism; Proto-Oncogene Proteins c-fyn; Proto-Oncogene Proteins c-yes; Proto-Oncogene Proteins pp60(c-src)/antagonists &; inhibitors/genetics/*metabolism; Tyrphostins/pharmacology; src-Family Kinases/antagonists & inhibitors/*metabolism; Titel: pp60(c-src) and related tyrosine kinases: a role in the assembly and reorganization of matrix adhesions
Role of integrins and focal adhesion kinase in the orientation of dermal fibroblasts exposed to cyclic strain.: Stretch is applied to skin under normal physiolo
Gentaur molecular products has all kinds of products like :search , Ray Biotech \ Recombinant Human Active Focal Adhesion Kinase \ 228-10439-3 for more molecular products just contact us
Focal adhesions are dynamic structures in which traction forces are exerted against the substratum during cell migration and are sites for the organization of signaling complexes. Palazzo and Gundersen discuss how focal adhesions may also be the site of cross-talk between the actin-based and microtubule-based cytoskeletons. Microtubules appear to deliver factors that can regulate the formation and dissolution of focal adhesions, whereas focal adhesions contribute to microtubule localization and stability.. ...
This is a major development for us, and I am looking forward to the experience and expertise that Dr. Cance will bring to our team, said Dr. Kraft. His leadership in Phoenix will be pivotal to enhance our partnership with Dignity Health and our efforts to impact the entire state of Arizona when it comes to fighting cancer.. Dr. Cance will be responsible for developing disease-focused clinical groups on the Phoenix campus, including recruiting physicians and organizing them into disease-oriented teams, as well as integration with the Tucson campus and developing one Cancer Center in two sites.. Dr. Cance, Physician-Scientist. Dr. Cances research interests focus on focal adhesion kinase (FAK), a critical survival signal in cancer and a promising therapeutic target being evaluated in several clinical trials using kinase enzyme inhibitors. He was the first researcher to clone human FAK in 1993 and demonstrate its overexpression in almost all human cancers. Today, Dr. Cance is homing in on the ...
Affinity determination:. Purified activated FAK kinase domain (amino acids 410-689) is reacted with 50 μM ATP, and 10 μg/well of a random peptide polymer of Glu and Tyr (molar ratio of 4:1), poly(Glu/Tyr) in kinase buffer (50 mM HEPES, pH 7.5, 125 mM NaCl, 48 mM MgCl2) for 15 min. Phosphorylation of poly(Glu/Tyr) is challenged with serially diluted compounds at 1/2-Log concentrations starting at a top concentration of 1 μM. Each concentration is run in triplicate. Phosphorylation of poly(Glu/Tyr) is detected with a general anti-phospho-tyrosine (PY20) antibody, followed by horseradish peroxidase-conjugated goat anti-mouse IgG antibody. The standard horseradish peroxidase substrate 3, 3 ...
Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the ...
Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the ...
The goal of this study was to determine if nanoNewton scale forces applied through specific ECM-integrin focal adhesion sites could induce myogenic-like micromechanical events from single mVSMCs. Our results indicate that forces applied to an FN-induced focal adhesion site induced mVSMCs to respond with a micromyogenic event. The micromyogenic event was dependent on interactions with α5β1-integrin, αvβ3-integrin, the actin cytoskeleton, and cSrc activity. To our knowledge, this is the first study using AFM technology to quantitatively measure the mechanical responses to applied force at single focal adhesion sites formed with specific ECM proteins. In contrast to FN, force applied to focal adhesion sites induced with CNI, VN, or LN were not able to elicit the micromyogenic event, suggesting that FN could be of particular relevance to the mechanosensing and transducing pathways in mVSMCs.. In this study, we estimated the scales of time and pulling force to mimic those approximated to occur at ...
Clinical evidence implicates FAK in the development and progression of OSCC (24). Although FAK expression is restricted to the proliferative basal cell layer in healthy human oral epithelia, full-thickness FAK protein is present in premalignant OIN lesions (24). Notably, FAK contributes to essential aspects of OIN malignant transformation by facilitating basement membrane invasion and inappropriately sustaining proliferation (25). Our data demonstrate that local delivery achievable levels of 4-HPR (11) inhibit FAKs prosurvival, mobility-enhancing functions in a spectrum of cultured oral human keratinocytes that range from normal to HPV E6/E7-transduced to malignant to metastatic.. All cell lines used in this study contained subpopulations that coexpressed cytokeratin and vimentin; findings consistent with the epithelial-to-mesenchymal transition (26). Our migration and invasion data show that 4-HPR suppressed this mobile phenotype. Also, 4-HPR treatment resulted in an intracellular gradient ...
Cancer Therapeutics CRC Pty Ltd is developing small molecule focal adhesion kinase (FAK) inhibitors for the treatment of metastatic cancers. Focal adhesion
Cancer cell expression of the T-cell co-stimulatory molecule CD80, or treatment with agonistic antibodies targeting the T-cell co-stimulatory receptors OX-40 or 4-1BB, enhances the anti-tumor activity of FAK inhibition.
Therefore, IL 17 derived from direct contact between FLSs from RA patients and CD4 T cells, as well as that secreted by Th17 polarized cells, can induce IL 32 expres sion in FLSs from RA patients. In both cases, IL 32 expression was arrested by IL 17 blockade. These results demonstrate that IL 17, an important cytokine in RA, has a direct role Nilotinib clinical in IL 32 expression by the FLSs of RA patients. IL 32 induced the production of IL 17 in human CD4 T cells and differentiation of Th17 cells Because IL Inhibitors,Modulators,Libraries 32 can induce inflammatory cytokines, we next assessed the IL 17 production by IL 32. To determine whether IL 32 induces IL 17 production, CD4 T cells from human PBMCs were cultured with membrane bound anti CD3 antibody to activate TCRs and the expression of IL 17 increased when was stimulated with IL 32.. CD4 T cells from healthy donors were differentiated using anti CD3, anti CD28, anti IL 4, and anti IFN g, antibodies, and IL 1b and IL 6. FACS analysis ...
Atat rk niversitesi Di Hekimli i Fak ltesinin resmi yay n organ d r. Y lda 4 kez yay mlan r.. T B TAK/ULAKB M taraf ndan dizinlenmektedir.. T rk Di Hekimli i Birli i S rekli Di Hekimli i E itim (TDB-SDE) Y ksek Kurulu Taraf ndan Kredilendirilmi tir. ISSN 1300-9044. Dergimiz ilk olarak 1986da bas lm t r, 1993 y l ndan beri d zenli olarak yay nlanmaktad r.. T rkiye At f Dizinine kay tl d r.. Anahtar kelimelerin T rkiye Bilim Terimleri (http://www.bilimterimleri.com)nden se ilmesi gerekmektedir.. ...
Atat rk niversitesi Di Hekimli i Fak ltesinin resmi yay n organ d r. Y lda 4 kez yay mlan r.. T B TAK/ULAKB M taraf ndan dizinlenmektedir.. T rk Di Hekimli i Birli i S rekli Di Hekimli i E itim (TDB-SDE) Y ksek Kurulu Taraf ndan Kredilendirilmi tir. ISSN 1300-9044. Dergimiz ilk olarak 1986da bas lm t r, 1993 y l ndan beri d zenli olarak yay nlanmaktad r.. T rkiye At f Dizinine kay tl d r.. Anahtar kelimelerin T rkiye Bilim Terimleri (http://www.bilimterimleri.com)nden se ilmesi gerekmektedir.. ...
Pages 149-154 Pancarcı ŞM, Kaçar C, Öğün M, Güngör Ö, Gürbulak K, Oral H, Karapehlivan M, Çitil M DOI : 10.9775/kvfd.2007.26-A ...
Normal FAK is a tyrosine kinase that gets recruited to focal adhesion sites and plays a key role in directed cell movement. ... Fyn is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been ... Fyn is a tyrosine-specific phospho-transferase that is a member of the Src family of non-receptor tyrosine protein kinases. ( ... This family also includes Abl, Src, focal adhesion kinase and Janus kinase.) Fyn is located downstream of several cell surface ...
"Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits ... The protein encoded by this gene belongs to the src family kinases. This protein is similar to the src kinase associated ... serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells". ... Kouroku Y, Soyama A, Fujita E, Urase K, Tsukahara T, Momoi T (November 1998). "RA70 is a src kinase-associated protein ...
... protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by ... Lineage for Protein: Focal adhesion kinase 1 Q00944 "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". Guan JL, Shalloway D ( ... a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase". ... "Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation". Nature ...
... mitogen-activated kinase activity through a pathway that involves related adhesion focal tyrosine kinase and protein kinase C ... receptor is coupled to mitogen-activated protein kinase via protein kinase C and epidermal growth factor receptor kinase". The ... Syk and ZAP-70 tyrosine kinases in TCR-mediated phosphorylation of the adapter protein Shc". European Journal of Immunology. 28 ... Protein TFG is a protein that in humans is encoded by the TFG gene. TFG (gene) has been shown to interact with PLSCR1. GRCh38: ...
... lymphocyte-specific protein tyrosine kinase (Lck), focal adhesion kinase (FAK) and fibroblast growth factor receptor 3 (FGFR3) ... Masitinib is a tyrosine kinase inhibitor which inhibits tyrosine kinases, enzymes responsible for the activation of many ... Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumours in animals, specifically dogs. Since its ... proteins by signal transduction cascades. Specifically, masitinib targets the receptor tyrosine kinase c-Kit which is found to ...
... also known as PTK2 protein tyrosine kinase 2 (PTK2). Focal adhesions are multi-protein intracellular signalling complexes that ... the focal adhesion targeting domain is a conserved protein domain that was first identified in focal adhesion kinase (FAK), ... Hayashi I, Vuori K, Liddington RC (February 2002). "The focal adhesion targeting (FAT) region of focal adhesion kinase is a ... Focal adhesions form and dissipate as cells attach and detach from matrix during cell adhesion and cell migration. The FAK ...
... focal adhesion kinase), due to its aforementioned presence in cellular focal adhesions. The protein tyrosine kinase pp125 is ... Protein tyrosine kinase plays a role in this task, too. A protein tyrosine kinase called pp125 is likely at hand in the ... This protein tyrosine kinase is up to about 70% unique compared to some other protein tyrosine kinases, a figure that is unlike ... Most tyrosine kinases have an associated protein tyrosine phosphatase, which removes the phosphate group. Protein kinases are a ...
The proteins that bind to paxillin are diverse and include protein tyrosine kinases, such as Src and focal adhesion kinase (FAK ... a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase". ... "Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion kinase in cardiac remodeling". The Journal of ... "Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol ...
Wilks (1989). "Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction". PNAS. 86 (5 ... this domain is also found in the focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine ... The four JAK family members are: Janus kinase 1 (JAK1) Janus kinase 2 (JAK2) Janus kinase 3 (JAK3) Tyrosine kinase 2 (TYK2) ... Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the ...
"A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine- ... "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". J. Biol. Chem. ... "Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain". Nat. Cell Biol. 3 ... A senescence-related protein, with focal adhesion kinase". J. Biol. Chem. 273 (41): 26516-21. PMID 9756887. doi:10.1074/jbc. ...
... increased tyrosine phosphorylytion of the focal adhesion kinase, and activation and nuclear translocation of mitogen-activated ... Experimental medications: sorafenib a combined Tyrosine protein kinases inhibitor. Scheduling of drug treatments and ... The ECM protein tenascin C (TNC) is up-regulated in metastatic breast cancer. TNC is an adhesion-modulating extracellular ... Integrin-mediated tumor cell adhesion to ECM proteins can trigger signal transduction and cause upregulation of gene expression ...
"Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". J. Biol. Chem. ... "The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to ... "Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol ... "Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase ...
Janus kinase 2, TYK2, and focal adhesion kinase as well as other tyrosine-phosphorylated proteins, including BCAR1, DOK1, beta- ... "Phosphorylated alpha-actinin and protein-tyrosine phosphatase 1B coregulate the disassembly of the focal adhesion kinase x Src ... Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the ... Receptor Kinase Activity by Protein Tyrosine Phosphatase 1B (PTP-1B) and Enhanced IGF-I-Mediated Suppression of Apoptosis and ...
The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). ... GRB7 is an SH2-domain adaptor protein that binds to receptor tyrosine kinases and provides the intra-cellular direct link to ... Han DC, Shen TL, Guan JL (Sep 2000). "Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase ... Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of ...
"Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase ... "Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase". J. Biol. ... Yoshida K, Kufe D (December 2001). "Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase C delta in ... "Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine ...
"A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine- ... "A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine- ... 2006). "JSAP1/JIP3 cooperates with focal adhesion kinase to regulate c-Jun N-terminal kinase and cell migration". J. Biol. Chem ... C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene. The protein ...
... when a receptor tyrosine kinase is activated, integrins co-localise at focal adhesion with the receptor tyrosine kinases and ... So the focal adhesions contain integrin ligand, integrin molecule, and associate plaque proteins. Binding is propelled by ... These act by regulating kinases such as FAK (focal adhesion kinase) and Src kinase family members to phosphorylate substrates ... in cell signaling by modulating the cell signaling pathways of transmembrane protein kinases such as receptor tyrosine kinases ...
... form focal adhesions with the substratum, linking them to the cell surface. Many types of migrating cells display ... Growth factors bind to receptor tyrosine kinases resulting in the polymerization of actin filaments, which, when cross-linked, ... Khurana S, George SP (September 2011). "The role of actin bundling proteins in the assembly of filopodia in epithelial cells". ... Rho activity also results in activation by phosphorylation of ezrin-moesin-radixin family proteins that link actin filaments to ...
... a member of focal adhesion kinase family. As a substrate for a tyrosine kinase in lymphoid cells, this protein may also ... encoded by this gene is preferentially expressed in hematopoietic cells and is most homologous to the focal adhesion protein, ... 2003). "Leupaxin is a critical adaptor protein in the adhesion zone of the osteoclast". J. Bone Miner. Res. 18 (4): 669-85. doi ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
The protein encoded by this gene belongs to the tensin family. Tensin is a focal adhesion molecule that binds to actin ... "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin". Biochem ... "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin". Biochem ... TENC1 has been shown to interact with AXL receptor tyrosine kinase. GRCh38: Ensembl release 89: ENSG00000111077 - Ensembl, May ...
This binding protein links Cdk5 and c-Abl, a tyrosine kinase. Active c-Abl phosphorylates CDK5 on tyrosine 15, a process ... Cdk5 also phosphorylates Focal adhesion kinase (FAK). This may stimulate nuclear translocation, which plays an important role ... "A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline-directed protein ... The Cdk5 kinase has an original design as well. Cdk5 belongs to the eukaryotic protein kinases (ePKs). A crystal structure of ...
... and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase". J. Biol. Chem. 277 (14): 12463-73. doi: ... 1999). "nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding ... Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene. RAPGEF2 is a cyclic AMP ... The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 4 (2): 141-50. ...
... and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase". The Journal of Biological Chemistry. 277 ( ... Diviani D, Soderling J, Scott JD (November 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho- ... Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins ... RhoGEF12 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 ...
... extracellular signal-regulated kinase, focal adhesion kinase, and other non-receptor tyrosine kinases. During fetal development ... It forms links with several protein kinases associated with cell locomotion, for example, ... The introduction of protein-based cross-links, the introduction of free-radical scavenging molecules such as sorbitol, and ... Hyaluronic acid is synthesized by a class of integral membrane proteins called hyaluronan synthases, of which vertebrates have ...
"Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility". Mol. Cell. Biol. 19 ... "Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in ... PTPN11 is a protein tyrosine phosphatase (PTP) Shp2. PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs ... Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology ...
"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 ... "Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces ... 1994). "Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src". Mol. Cell. Biol ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... Tyrosine:. *protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase. *Sh2 domain-containing protein tyrosine ... Protein kinase C ('PKC'). is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
The SH3 domain is a point of contact with polyproline sequences on focal adhesion kinase (FAK). or the related kinase PTK2B, ... Once phosphorylated by SRC or other kinases, these tyrosine motifs are bound by the SH2 domains of signaling proteins. ... allowing the CAS protein to function as a scaffold for other proteins including CRK proteins and C3G, a guanine nucleotide ... PTP-PEST, a soluble protein tyrosine phosphatase that is ubiquitously expressed in mice both during embryonic development and ...
2001). "Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain". Nat. Cell ... Cytoplasmic tyrosine-protein kinase BMX is an enzyme that in humans is encoded by the BMX gene. Tyrosine kinases are either ... "Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain". Nat. Cell Biol. 3 ... "The Bmx tyrosine kinase induces activation of the Stat signaling pathway, which is specifically inhibited by protein kinase ...
This interaction leads to a signaling cascade which activates focal adhesion kinases (FAK) which are then converted to its ... F11 and receptor tyrosine kinases (specially during the development of the nervous system). The six Ig motif of the L1 protein ... This protein, of 200-220 kDa, is a neuronal cell adhesion molecule with a strong implication in cell migration, adhesion, ... "L1CAM - Neural cell adhesion molecule L1 precursor - Homo sapiens (Human) - L1CAM gene & protein". www.uniprot.org. Retrieved ...
c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein ... It also regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion, and regulates matrix ... A number of tyrosine kinase inhibitors that target c-Src tyrosine kinase (as well as related tyrosine kinases) have been ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ...
... a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces ... Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ... "A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle". ... "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ...
"Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase". Nature Cell Biology. 7 (6): ... MAP-1 proteins consists of a set of three different proteins: A, B and C. The C protein plays an important role in the ... Although the tubulin carboxypeptidase has yet to be identified, the tubulin-tyrosine ligase (TTL) is known. Delta2: the removal ... including the motor proteins kinesin and dynein, microtubule-severing proteins like katanin, and other proteins important for ...
Coutts AS, MacKenzie E, Griffith E, Black DM (2003). "TES is a novel focal adhesion protein with a role in cell spreading". J. ... 2003). "Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase". J. Biol. Chem. 278 ... 2000). "Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins ... Protein enabled homolog is a protein that in humans is encoded by the ENAH gene. ENAH (gene) has been shown to interact with ...
"The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome". Nat. Cell ... "Fyn and Lck tyrosine kinases regulate tyrosine phosphorylation of p105CasL, a member of the p130Cas docking protein family, in ... Focal adhesion targeting (FAT) domain The FAT-like C-terminal domain is highly conserved in focal adhesion proteins, and ... Hayashi I, Vuori K, Liddington RC (2002). "The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix ...
"The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome". Nature ... "Tyrosine phosphorylation of Crk-associated substrates by focal adhesion kinase. A putative mechanism for the integrin-mediated ... These include association with FAK and Src family kinases at focal adhesions to transmit integrin-initiated signals to ... Cas scaffolding protein family member 4 is a protein that in humans is encoded by the CASS4 gene. CASS4 (Crk associated ...
"Targeting Focal Adhesion Kinase Renders Pancreatic Cancers Responsive to Checkpoint Immunotherapy". Nature Medicine. 22 (8): ... The defective BCR-ABL gene makes it possible to manufacture an abnormal version of an enzyme of the Tyrosine Kinase type ... ECM is a mixture of cells (immune, fibroblasts, etc.) dispersed in proteins, most of them collagen. It surrounds the tumor. It ... focal adhesions (all intercellular junctions and ETM / cells), membrane, CSK, etc. also support the production of energy. ...
... response to tyrosine kinase inhibitor in; 211980; EGFR Nonsmall cell lung cancer, somatic; 211980; IRF1 Nonsmall cell lung ... focal segmental, 1; 603278; ACTN4 Glomerulosclerosis, focal segmental, 2; 603965; TRPC6 Glomerulosclerosis, focal segmental, 3 ... GATA1 Leukocyte adhesion deficiency; 116920; ITGB2 Leukocyte adhesion deficiency, type III; 612840; KIND3 Leukodystrophy, adult ... HRG Thrombophilia due to protein C deficiency, autosomal dominant; 176860; PROC Thrombophilia due to protein C deficiency, ...
... in hepatocellular carcinoma cells resulted in dephosphorylation of tyrosine residues on the molecule focal adhesion kinase ... These interactions allow DLC1 to co-localize along with these proteins to focal adhesions at the periphery of the cell, where ... The activity of RhoA regulates the formation of actin stress fibers and focal adhesions - complexes of many proteins located at ... DLC1 is also involved in the formation of focal adhesions, so loss of DLC1 leads to reduced cell adhesion and increased ...
... ligand 12-induced focal adhesion kinase activation and segregation into membrane domains is modulated by regulator of G protein ... 2001). "GIPC and GAIP Form a Complex with TrkA: A Putative Link between G Protein and Receptor Tyrosine Kinase Pathways". Mol. ... Druey KM, Blumer KJ, Kang VH, Kehrl JH (May 1996). "Inhibition of G-protein-mediated MAP kinase activation by a new mammalian ... Regulator of G-protein signaling 1 is a protein that in humans is encoded by the RGS1 gene. This gene encodes a member of the ...
Shofuda T, Shofuda K, Ferri N (2004). "Cleavage of focal adhesion kinase in vascular smooth muscle cells overexpressing ... Wang SC, Lien HC, Xia W (2004). "Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB- ... one which encodes a membrane-bound form and another a soluble form of the protein. Both forms of the protein activate MMP2 by ... Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal ...
"Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1)". ... Because inhibition of RhoA results in a decrease in both stress fibers and focal adhesion, cell motility is increased. P27 can ... When p27 is phosphorylated by Src at tyrosine 74 or 88 it ceases to inhibit cyclinE-cdk2. Src was also shown to reduce the half ... It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded ...
"The adaptor protein Nck links receptor tyrosine kinases with the serine-threonine kinase Pak1". The Journal of Biological ... "Activation of p21-activated kinase 1 is required for lysophosphatidic acid-induced focal adhesion kinase phosphorylation and ... ARG-binding protein 2γ, hepatitis B virus X protein, STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl ... PAK proteins, a family of serine/threonine p21-activated kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as ...
"The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions". ... "The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has ... "The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions". ... Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene. The protein encoded by ...
... and modulate the activity of focal adhesion kinase (FAK). Endostatin is a 20 kDa fragment of collagen XVIII. The major role of ... 2005). "Distinct roles of the receptor tyrosine kinases Tie1 and Tie2 in blood vessel formation". Cell. 123 (2): 291-304. doi: ... and interfering with various angiogenic related proteins such as integrins and serine/threonine-specific protein kinases. ... The cell uses limited proteolytic activity at sites of individual focal adhesions via the formation of multiprotein complexes. ...
... on the surface of CHO cells resulted in tyrosine phosphorylation of pp125FAK and induced mitogen-activated protein kinase ... which in adhesive cells is mainly focal adhesions. Integrin beta-1 mutants lose the ability to target to sites of focal ... Liliental J, Chang DD (Jan 1998). "Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit". The ... Burridge K, Chrzanowska-Wodnicka M (1996). "Focal adhesions, contractility, and signaling". Annual Review of Cell and ...
Additionally, phosphorylation by protein kinase A and dephosphorylation by alkaline phosphatase have been found to positively ... microtubule-associated proteins, and neurofilaments. It may also damage ion channels, other enzymes, cell adhesion molecules, ... phenylalanine and tyrosine) at the P1 position. Arguably, the best currently available fluorogenic calpain substrate is (EDANS ... and MDL28170 significantly reduced the size of damaged infarct tissue in a rat focal ischemia model. Also, calpain inhibitors ...
"Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase". The ... Goldmann WH (2003). "p56(lck) Controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK))". ... Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling ... Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 kDa protein that is found inside specialized cells of the immune ...
Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins. Janus tyrosine ... Non-receptor tyrosine-protein kinase TYK2. Protein-tyrosine phosphatases PTPN3 and PTPN4, enzymes that appear to act at ... Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E. Caenorhabditis elegans protein phosphatase ptp-1. Chishti ... Ezrin, moesin, and radixin are highly related proteins (ERM protein family), but the other proteins in which the FERM domain is ...
Ren R, Ye ZS, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding ... competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase". Molecular and Cellular Biology ... Ren R, Ye ZS, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding ... Shi CS, Tuscano J, Kehrl JH (February 2000). "Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase ...
"Focal adhesion kinase in netrin-1 signaling". Nat. Neurosci. 7 (11): 1204-12. doi:10.1038/nn1330. PMID 15494733. S2CID 2901216 ... The slit proteins have repulsive functions, as opposed to netrins, and are mediated by the transmembrane protein Robo. Axonal ... Ren XR, Hong Y, Feng Z, Yang HM, Mei L, Xiong WC (2008). "Tyrosine phosphorylation of netrin receptors in netrin-1 signaling". ... This theoretically results in 13 correctly sliced, putatively good proteins. The typical DCC protein has one signal peptide ...
In particular, Schlaepfer is well known for his studies on focal adhesion kinase (FAK). Schlaepfer received his PhD in ... a pioneer in the study of protein-tyrosine phosphorylation, where his work focused on FAK. In 1995, Schlaepfer won the Santa ... His early research focused on signaling by protein kinases, with a subsequent focus on the proteins that regulate the turnover ... Integrin-mediated signal transduction linked to Ras Pathway by Grb2 Binding to Focal adhesion kinase. Nature 372: 786-791. Ilic ...
Talin and focal adhesion kinase (FAK) are two of the proteins that present FERM domains. Calponin homology (CH) domain CH ... in cell signaling proteins like protein tyrosine kinases and the growth factor receptor bound protein 2 (Grb2). Phosphotyrosine ... complex Protein domain dynamics Protein flexibility Protein structure Protein-protein interaction prediction Protein-protein ... Protein-Protein Interaction Databases Library of Modulators of Protein-Protein Interactions (PPI) Proteins and Enzymes at ...
Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin.. S K Hanks, M B Calalb, M ... Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. ... Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. ... Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. ...
Focal Adhesion Protein-Tyrosine Kinases*Focal Adhesion Protein-Tyrosine Kinases. *Focal Adhesion Protein Tyrosine Kinases ... "Focal Adhesion Protein-Tyrosine Kinases" by people in this website by year, and whether "Focal Adhesion Protein-Tyrosine ... Protein-Tyrosine Kinases [D08.811.913.696.620.682.725]. *Focal Adhesion Protein-Tyrosine Kinases [D08.811.913.696.620.682. ... "Focal Adhesion Protein-Tyrosine Kinases" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus ...
Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK.. M D Schaller ... We have recently isolated a cDNA encoding a unique, focal adhesion-associated protein tyrosine kinase (FAK) that is a component ... Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. ... Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. ...
Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion. In: Scientific Reports. ... Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion. Scientific Reports. 2017 ... Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion. / Durand, Nisha; Bastea ... title = "Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion", ...
... is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes. It has been shown that ... FAK is a member of the FAK subfamily of protein tyrosine kinases that included PYK2 but lacks significant sequence similarity ... FAK tyrosine kinase activity can be activated, which plays a key important early step in cell migration. ... FAK is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. ...
downstream signaling molecules cellular function in signal transduction focal adhesion protein tyrosine kinases. Medical ... PaxillinFocal Adhesion Protein-Tyrosine KinasesFocal Adhesion Kinase 1TyrosineProtein-Tyrosine KinasesProtein Tyrosine ... Focal AdhesionsPaxillinFocal Adhesion Protein-Tyrosine KinasesSignal TransductionFocal Adhesion Kinase 1TyrosineProtein- ... Focal AdhesionsPaxillinFocal Adhesion Protein-Tyrosine KinasesSignal TransductionFocal Adhesion Kinase 1TyrosineProtein- ...
Focal Adhesion Kinase 1 * Focal Adhesion Protein-Tyrosine Kinases * PTK2 protein, human ... interacts with the focal adhesion kinase (FAK), a kinase implicated in regulating cell adhesion and migration. FAK was ... Focal adhesion kinase in netrin-1 signaling Nat Neurosci. 2004 Nov;7(11):1204-12. doi: 10.1038/nn1330. Epub 2004 Oct 17. ... Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth ...
Here, we develop a model system of focal adhesion disassembly based on the finding that microtubule regrowth after nocodazole ... Imaging studies implicate microtubule targeting of focal adhesions in focal adhesion disassembly, although the molecular ... Protein-Tyrosine Kinases * Focal Adhesion Kinase 1 * Focal Adhesion Protein-Tyrosine Kinases ... Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase Nat Cell Biol. 2005 Jun;7(6): ...
Focal Adhesion Protein-Tyrosine Kinases. Grant support. *R21 CA128660-01/CA/NCI NIH HHS/United States ... Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. Stress, ... Focal Adhesion Protein-Tyrosine Kinases/physiology. *Mammary Glands, Animal/growth & development. *Mammary Glands, Animal/ ...
Hyaluronate activates tyrosine phosphorylation of cellular proteins including focal adhesion kinase via CD44 in human glioma ... Hyaluronate activates tyrosine phosphorylation of cellular proteins including focal adhesion kinase via CD44 in human glioma ... Hyaluronate activates tyrosine phosphorylation of cellular proteins including focal adhesion kinase via CD44 in human glioma ... Hyaluronate activates tyrosine phosphorylation of cellular proteins including focal adhesion kinase via CD44 in human glioma ...
... cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including ... in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell ... Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also ... Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. ...
... creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the ... Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the ... Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone ... focal adhesion Source: MGI. *glutamatergic synapse Source: MGI. *membrane raft Source: MGIInferred from direct assayi*12388746 ...
Background Focal adhesion Kinase (FAK) is a nonreceptor proteins tyrosine kinase that is overexpressed in tumors and plays a ... Background Focal adhesion Kinase (FAK) is a nonreceptor proteins tyrosine kinase. May 18, 2017 ... Mitogen-Activated Protein Kinase *Mitogen-Activated Protein Kinase Kinase *Mitogen-Activated Protein Kinase-Activated Protein ... Inhibition of the 90 kDa heat-shock proteins (HSP90) network marketing leads ...
... of focal adhesions in cultured retinal glia demonstrate an important role for tyrosine kinase activity in regulating focal ... Focal adhesions consist of clustered integrins and associated proteins, referred to as focal adhesion proteins. These proteins ... Immunolocalization of Focal Adhesion Proteins in XR1 Retinal Glial Cells. Focal adhesions are a discrete streak-like complex of ... To identify focal adhesions and characterize the relationship among focal adhesion proteins and the F-actin cytoskeleton, we ...
... is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null ... Focal Adhesion Protein-Tyrosine Kinases / metabolism*. Gene Knockdown Techniques. Humans. Integrin alpha5beta1 / metabolism*. ... Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and ... EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases; F8VB5M810T/Tetracycline ...
focal adhesion kinase 2. proline-rich tyrosine kinase 2. protein kinase B. related adhesion focal tyrosine kinase. NP_004094.3 ... Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase. smart00219. Location:425 → 679. TyrKc; Tyrosine kinase ... Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase. smart00219. Location:425 → 679. TyrKc; Tyrosine kinase ... Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase. smart00219. Location:425 → 679. TyrKc; Tyrosine kinase ...
Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A ... pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A 1992;89: ... Focal adhesion kinase (FAK) is a nonreceptor type tyrosine kinase composed of ∼1,030 amino acids that regulates integrin and ... Dual Tyrosine Kinase Inhibitor for Focal Adhesion Kinase and Insulin-like Growth Factor-I Receptor Exhibits Anticancer Effect ...
Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol. 1993 3: 258-62. ... Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by ... Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med 2016: Aug 22. (8) ... also holds worldwide rights to the tumor microenvironment-targeting focal adhesion kinase (FAK) inhibitors defactinib (VS-6063 ...
Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol. 1993 3: 258-62. ... Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by ... Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med 2016: Aug 22(8) 851- ... include focal adhesion kinase (FAK) inhibitors defactinib (VS-6063) and VS-4718, and dual PI3K/mTOR inhibitor VS-5584. ...
Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol. 1993 3: 258-62. ... Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by ... Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med 2016: Aug 22(8) 851- ... In addition to duvelisib, Verastem also holds worldwide rights to the tumor microenvironment-targeting focal adhesion kinase ( ...
Cloning and characterization of cell adhesion kinase beta, a novel protein-tyrosine kinase of the focal adhesion kinase ... Showing Protein Protein-tyrosine kinase 2-beta (HMDBP01425). IdentificationBiological propertiesGene propertiesProtein ... Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions. J Biol Chem. 1998 ... Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits ...
EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases; EC 2.7.10.2/src-Family Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt ... Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors, biosynthesis. Humans. Interleukin-8 / biosynthesis*, ... EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.6.5.2/RND3 protein, ... Mitogen-Activated Protein Kinase 1 / biosynthesis. Mitogen-Activated Protein Kinase 3 / biosynthesis. Muscle, Smooth / drug ...
Focal Adhesion Protein-Tyrosine Kinases); EC 3.4.21.1 (Chymotrypsin); EC 3.4.25.1 (Proteasome Endopeptidase Complex). ... Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is ... FHOD3 protein, human); 0 (Fetal Proteins); 0 (Microfilament Proteins); 0 (Nuclear Proteins); 0 (gamma Catenin). ... 0 (Actins); 0 (DNA-Binding Proteins); 0 (Hip1r protein, mouse); 11003-00-2 (Actinin); 114899-12-6 (Clathrin Heavy Chains); EC ...
1992). Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. ... 1992). Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc. Nat. Acad. ... 1992). pp125FAK, a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc. Nat. Acad. Sci. USA ... 1993). Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. Mol. ...
pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A 1992;89: ... Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem ... Using a fluorescent, bead-based technology to profile activated tyrosine kinases, we identified focal adhesion kinase (FAK, ... we evaluated the tyrosine kinase landscape in Ewing sarcoma cell lines and identified focal adhesion kinase (FAK/PTK2) as an ...
1992) Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. ... 1995) Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase. J Biol Chem 270:17437-17441. ... Tyrosine kinase assays. THP1 monocytes were stimulated with Aβ25-35, and tyrosine-phosphorylated proteins were ... Aβ-induced tyrosine kinase activity was measured in parallel assays by an enzymatic assay of the tyrosine kinases by ...
... focal adhesion kinase abbreviated? p125FAK stands for proteins is the 125-kDa focal adhesion kinase. p125FAK is defined as ... proteins is the 125-kDa focal adhesion kinase rarely. ... Focal adhesion kinase; kDa intracellular protein tyrosine ... Focal Adhesion Kinase is a 125 kDa non-receptor protein; Focal Adhesion Kinase plays a; Primary Antibodies Secondary Antibodies ... a href=https://www.acronymattic.com/proteins-is-the-125_kDa-%22focal-adhesion-kinase-(p125FAK).html,p125FAK,/a,. ...
Focal Adhesion Kinase 2); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases); EC 3.6.5.2 (rap1 GTP-Binding Proteins); EC 3.6 ... 0 (Bacterial Proteins); 0 (Protozoan Proteins); EC 3.6.5.2 (Monomeric GTP-Binding Proteins); EC 3.6.5.2 (Rap1 protein, mouse); ... TERF2IP protein, human); 0 (Telomere-Binding Proteins); EC 3.6.5.2 (Rap1 protein, mouse); EC 3.6.5.2 (rap1 GTP-Binding Proteins ... 0 (Integrin beta1); 0 (Nerve Tissue Proteins); 0 (SHARPIN protein, human); 0 (Talin); 0 (Ubiquitins); EC 3.6.1.- (RRAS protein ...
Targeted effector; protein tyrosine kinase; interferes with cell signaling at focal adhesions. +. 10347. 11753. 469. 8.68. ... Targeted effector; Ser Thr kinase. +. 5204. 7402. 733. 6.53. 81.74 yopJ(yopP). Targeted effector; causes apoptosis in ...
Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, displays phosphorylation-dependent localization in the ... 2007) Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics. J Cell Biol 176:667-680. ... 2007) Focal adhesion kinase is negatively regulated by phosphorylation at tyrosine 407. J Biol Chem 282:10398-10404. ... 2009) Focal adhesion kinase: Switching between GAPs and GEFs in the regulation of cell motility. Curr Opin Cell Biol 21:676-683 ...
  • We have recently isolated a cDNA encoding a unique, focal adhesion-associated protein tyrosine kinase (FAK) that is a component of an integrin-mediated signal transduction pathway. (asm.org)
  • Downstream signaling molecules cellular function in signal transduction focal adhesion protein tyrosine kinases. (lookformedical.com)
  • The N-terminal helix contains a phosphorylatable tyrosine (Y925) implicated in signal transduction . (lookformedical.com)
  • Phosphorylation of proteins by kinases is an important mechanism for communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division. (wikipedia.org)
  • Furthermore, tyrosine kinases function in many signal transduction cascades wherein extracellular signals are transmitted through the cell membrane to the cytoplasm and often to the nucleus, where gene expression may be modified. (wikipedia.org)
  • The receptor tyrosine kinases function in transmembrane signaling, whereas tyrosine kinases within the cell function in signal transduction to the nucleus. (wikipedia.org)
  • Lyn and Src family tyrosine kinases in general have been known to function in signal transduction pathways. (wikipedia.org)
  • Many of these proteins have been shown to play predominantly a structural role or are involved in signal transduction [ 36 ]. (hindawi.com)
  • The Zap70 protein tyrosine kinase controls TCR-linked signal transduction pathways and is critical for T cell development and responsiveness. (jimmunol.org)
  • Focal adhesion kinase (FAK) becomes tyrosine-phosphorylated during integrin-mediated cell adhesion and is believed to play important roles in integrin signal transduction (7,8). (scielo.br)
  • Signal transduction through mitogen-activated protein kinase (MAPK) cascades is thought to occur through the assembly of macromolecular complexes. (ebscohost.com)
  • Paxillin is also a "docking" protein involved in organizing the signal transduction complex. (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)
  • Taken together, paxillin may function as a structural protein to maintain the integrity of the SMC contractile apparatus and as a docking protein to potentially mediate signal transduction for SMC contraction, migration, proliferation, and possibly differentiation. (ahajournals.org)
  • Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2 , netrin receptors and LDL receptors. (rcsb.org)
  • Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways. (wikipedia.org)
  • Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. (abcam.com)
  • A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. (umassmed.edu)
  • Focal adhesion kinase (FAK) regulates integrin and growth factor-mediated signaling pathways to enhance cell migration, proliferation, and survival, and its up-regulation correlates malignant grade and poor outcome in several types of cancer. (aacrjournals.org)
  • Focal adhesion kinase (FAK) is a nonreceptor type tyrosine kinase composed of ∼1,030 amino acids that regulates integrin and growth factor signaling pathways, thereby playing an important role in cell proliferation, differentiation, and apoptosis ( 1 - 5 ). (aacrjournals.org)
  • Tyrosine kinases function in a variety of processes, pathways, and actions, and are responsible for key events in the body. (wikipedia.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)
  • 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)
  • 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)
  • The mechanistic pathways that link mechanical stimuli to biochemical signals in cardiac myocytes are presently unclear, but a growing body of evidence indicates that costameres (complex structures constituted by integrins and cytoskeletal proteins at the junction of sarcolemma and Z-discs) have a critical role in sensing and transducing mechanical stress into biochemical signals that coordinate growth responses to hypertrophic stimuli in both cardiac and skeletal muscle. (ahajournals.org)
  • 15-18 Data obtained in NRVMs have shown that Fak is also involved in the regulation of early gene transcription in response to hypertrophic agonists, 19-22 indicating that this kinase may function as a node for the convergence of multiple signaling pathways involved in the hypertrophic growth of cardiac myocytes. (ahajournals.org)
  • Annexin II was identified as an HE4 interacting protein.HE4 gene interference downregulated the expression of MAPK and the FOCAL adhesion signaling pathway-associated molecules MKNK2 and LAMB2, and HE4 protein supplementation reversed this effect.The binding interaction between HE4 and annexin II activates the MAPK and FOCAL adhesion signaling pathways, promoting ovarian cancer cell invasion and metastasis. (nih.gov)
  • The binding interaction between HE4 and annexin II activates the MAPK and FOCAL adhesion signaling pathways, promoting ovarian cancer cell invasion and metastasis. (nih.gov)
  • Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane, where it phosphorylates tyrosine residues on key targets involved in a variety of different signaling pathways. (wikipedia.org)
  • TCR signaling cascades connect extrinsic activation signals with actin polymerization pathways that regulate intracellular signaling, adhesion, and migration of T cells ( 2 , 3 ). (sciencemag.org)
  • Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. (scielo.br)
  • The project aims to use tandem mass spectrometry (LC/MS/MS) to assess the signaling pathways in tumors in order to quantitatively determine the drivers of cancers from cell receptors to downstream kinases. (harvard.edu)
  • The student will perform immunoprecipitations (IP) of key signaling nodes in cell and tumor lysates and then based on the quantitative mass spectrometry protein-protein interaction (PPI) data, validate the findings by choosing the appropriate single agent or combinations of tyrosine kinase inhibitor (TKI) drugs in order to both shut down the affected signaling pathways and kill the cancer cells. (harvard.edu)
  • 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)
  • Furthermore, we obtained numerous new findings concerning positive and negative regulations of SAPK pathways by protein phosphatases, adaptor and binding proteins, and docking interactions. (nii.ac.jp)
  • Both kinases act as critical mediators for the activation of signaling pathways that regulate cell migration, proliferation, and survival . (axonmedchem.com)
  • Non-receptor protein-tyrosine kinase implicated in signaling pathways involved in cell motility, proliferation and apoptosis. (bioon.com.cn)
  • Agrin can activate YAP in HSF possibly through the interactions with integrin mediated adhesion and Lrp4/MuSK receptor-mediated signaling pathways. (alliedacademies.org)
  • In addition, the functions of Agrin in those processes were proved to be related with its interactions with integrin mediated adhesion and low-density lipoprotein receptor-related protein-4 (Lrp4)/Muscle Associated Receptor Tyrosine Kinase (MuSK) receptor-mediated signaling pathways [ 9 ]. (alliedacademies.org)
  • Sekimoto H, Eipper-Mains J, Pond-Tor S, Boney CM. (alpha)v(beta)3 integrins and Pyk2 mediate insulin-like growth factor I activation of Src and mitogen-activated protein kinase in 3T3-L1 cells. (umassmed.edu)
  • Integrins play a central role in cellular adhesion and anchorage of the cytoskeleton and participate in the generation of intracellular signals, including tyrosine phosphorylation. (asm.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)
  • 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)
  • Integrins are transmembrane adhesion receptors that provide a functional link between the ECM and the actin cytoskeleton. (hindawi.com)
  • RGD-dependent integrins are a subgroup of adhesion receptors that specifically recognize the RGD motif, which is a three-amino-acid sequence (Arg-Gly-Asp) that is found in some ECM proteins. (hindawi.com)
  • Integrins also play important roles in blood clotting and wound healing by regulating platelet adhesion and aggregation. (hindawi.com)
  • Fyn is a protein, present in the signaling pathway of integrins, which activates ras. (wikipedia.org)
  • The SFKs 2 play a central role in the transduction of extracellular signals acting through activated RTKs, G-protein-coupled hormone receptors, and integrins to downstream cellular effectors ( 1 ). (aacrjournals.org)
  • Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. (scielo.br)
  • Interaction of integrins with the ECM proteins can induce tyrosine phosphorylation of many intracellular proteins. (scielo.br)
  • Focal adhesion kinase (FAK) is a tyrosine kinase found in focal adhesions, intracellular signalling complexes that are formed following engagement of the extracellular matrix by integrins. (embl.de)
  • Integrin-linked kinase (ILK) is the binding partner of β1 and β3 integrins, and has been ascribed essential roles in development, angiogenesis and tumourigenesis. (ebscohost.com)
  • Integrins and integrin-related proteins in cardiac fibrosis. (semanticscholar.org)
  • FAK is a nonreceptor protein tyrosine kinase that integrates signals from integrins and growth factor receptors to regulate cell proliferation, survival, migration, invasion, and cancer stem cell (CSC) renewal ( 1 - 3 ). (sciencemag.org)
  • Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. (umassmed.edu)
  • An important tyrosine kinase found in focal adhesions is the focal adhesion kinase (FAK). (hindawi.com)
  • FAK is a cytoplasmic tyrosine kinase found in focal adhesions of cells. (ebscohost.com)
  • Focal adhesion kinase (FAK) regulates multiple. (ebscohost.com)
  • CRK transmits signals to small G proteins through its SH3 domain binding target C3G and DOCK180 those can activate Rap /R-Ras and Rac , respectively, and regulates cell growth, adhesion, and motility. (atlasgeneticsoncology.org)
  • Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. (nih.gov)
  • One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. (wikipedia.org)
  • A recent study has shown that agrin regulates focal adhesion integrity in patients with hepatocellular carcinoma to promote the progression of tumor [ 8 ]. (alliedacademies.org)
  • Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. (uniprot.org)
  • 1988 ). Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. (biologists.org)
  • Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signaling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. (wikipathways.org)
  • These proteins are connected to intracellular proteins that include diverse signaling molecules recruited to sites of focal adhesion, and are also linked to the actin cytoskeleton (2). (scielo.br)
  • a and a ß subunit, with a long extracellular domain binding to the ECM, a transmembrane domain, and a short cytoplasmic domain that associates with the actin cytoskeleton and adaptor proteins (3). (scielo.br)
  • Focal adhesions are structures that anchor the actin cytoskeleton to extracellular matrix and FAK is thought to associate with matrix receptors called. (ebscohost.com)
  • The actin cytoskeleton is essential for cell adhesion and migration, functions important for tumor invasion. (asm.org)
  • Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. (rcsb.org)
  • 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)
  • 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)
  • Can modulate the effect of DAPK3 in reorganization of actin cytoskeleton and focal adhesion dissolution. (genecards.org)
  • Insulin stimulates spreading of skeletal muscle cells involving the activation of focal adhesion kinase, phosphatidylinositol 3-kinase and extracellular signal regulated kinases. (umassmed.edu)
  • The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (wikipedia.org)
  • In the present study, pharmacological and dominant-negative strategies were used to show that feeding a formulated diet containing increased amounts of salt to young male Sprague-Dawley rats induced the formation of an endothelial cell-signaling complex that contained proline-rich tyrosine kinase 2, c-Src (also known as pp60 c-src ), and phosphatidylinositol 3-kinase. (ahajournals.org)
  • In the setting of a high-salt diet, proline-rich tyrosine kinase 2 served as the scaffold for c-Src-mediated phosphatidylinositol 3-kinase activation. (ahajournals.org)
  • Phosphatidylinositol 3-kinase was the upstream activator of protein kinase B (Akt), which was responsible for phosphorylation of the rat endothelial isoform of NO synthase at S1176 and thereby promoted the increase in NO production. (ahajournals.org)
  • 22,24 Pyk2 has multiple binding partners that include c-Src, the 60-kDa protein of c-src (also known as pp60 c-src ), phosphatidylinositol 3-kinase (PI3-kinase), and Grb2. (ahajournals.org)
  • FAK, a non-receptor tyrosine kinase, interacts with a pool of intracellular signaling proteins, including c-Src, phosphatidylinositol 3-kinase (PI3-K), Rho GTPase family members, Grb2, and p130 CAS (6). (scielo.br)
  • Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. (rcsb.org)
  • Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. (uniprot.org)
  • The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. (nih.gov)
  • They are composed of many different molecules including adhesion receptors, signaling proteins (e.g., kinases, phosphatases, and adaptor proteins), and structural proteins (e.g., actin-binding proteins) [ 1 - 3 ]. (hindawi.com)
  • For cell-ECM adhesions, their assembly is initiated by the binding of integrin adhesion receptors to the ECM. (hindawi.com)
  • β 1 integrin was required for FAK independent activation of all three MAP kinases, whereas cross-talk between β 1 integrin and Ang II receptors mediated FAK dependent regulation of ERK1/2. (pubmedcentralcanada.ca)
  • At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. (wikipathways.org)
  • Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signaling. (wikipathways.org)
  • Interactions between growth factor receptors and adhesion molecules: breaking the rules. (wikipathways.org)
  • 22 This nonreceptor tyrosine kinase is typically activated by extracellular stress signals, such as shear stress, 23 but also by G protein-coupled receptors, such as the angiotensin type 1 receptor. (ahajournals.org)
  • Crk also binds to growth factor receptors such as EGFR or FGF, in addition to downstream signaling scaffold protein Gab1 which is mainly activated by HGF . (atlasgeneticsoncology.org)
  • this domain is also found in the focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine receptors and/or other kinases. (wikipedia.org)
  • 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)
  • Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. (genecards.org)
  • PKC-regulated myogenesis is associated with increased tyrosine phosphorylation of FAK, Cas, and paxillin, formation of Cas-CRK complex, and JNK activation. (umassmed.edu)
  • 1992 ). Tyrosine phosphorylation of paxillin and pp125FAKaccompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. (biologists.org)
  • 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)
  • Attachment of S. flexneri to CHO cells can elicit tyrosine phosphorylation of pp125 FAK and paxillin, localized accumulation of F-actin, vinculin, and talin, and activation of protein kinase C, which were all blocked by the treatment with C3 transferase. (rupress.org)
  • Paxillin and focal adhesion signalling. (wikipathways.org)
  • Paxillin, a focal adhesion protein, is a substrate for several tyrosine kinases such as src, FAK, and p120BRC/ABL. (fishersci.com)
  • The tyrosine phosphorylation of paxillin is affected by conditions that change cell-cell adhesion. (fishersci.com)
  • The binding of FAT to the focal adhesion protein, paxillin, requires the integrity of the helical bundle, whereas binding to another focal adhesion protein, talin, does not. (embl.de)
  • The expression of paxillin and its associated proteins was determined in injured arteries by Western blot analysis. (ahajournals.org)
  • eNOS gene transfer showed no effect on paxillin downregulation 2 days after injury but significantly enhanced the recovery of paxillin protein 5 days and 2 weeks after injury. (ahajournals.org)
  • Vinculin, a paxillin-binding protein, was not altered by vascular injury or by eNOS gene transfer. (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)
  • 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 7 8 9 Paxillin has multiple tyrosine phosphorylation sites that can be phosphorylated by csk, c-src, and FAK to form the src homology 2 domain (SH2). (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)
  • As a member of the LIM domain-containing proteins, paxillin may play an important role in the differentiation of vascular SMCs. (ahajournals.org)
  • In focal adhesion complex, Crk binds to p130Cas which possesses six Crk binding consensus sequences and to paxillin . (atlasgeneticsoncology.org)
  • A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. (wikipedia.org)
  • Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal) phosphate from nucleoside triphosphates (often ATP) to one or more amino acid residues in a protein substrate side-chain, resulting in a conformational change affecting protein function. (wikipedia.org)
  • Tyrosine kinases catalyze the phosphorylation of tyrosine residues in proteins. (wikipedia.org)
  • The phosphorylation of tyrosine residues in turn causes a change in the function of the protein that they are contained in. (wikipedia.org)
  • Phosphorylation at tyrosine residues controls a wide range of properties in proteins such as enzyme activity, subcellular localization, and interaction between molecules. (wikipedia.org)
  • proteins in the cytosol and proteins in the nucleus are phosphorylated at tyrosine residues during this process. (wikipedia.org)
  • Following engagement of TCR, the Zap70 undergoes phosphorylation on multiple tyrosine residues that are implicated in the regulation of its catalytic activity and interaction with signaling effector molecules downstream of the TCR. (jimmunol.org)
  • 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)
  • We have reported that tyrosine residues in FAK are dephosphorylated and FAK is degraded during mannitol-induced apoptosis in human neuroblastoma cells. (ebscohost.com)
  • The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. (reactome.org)
  • The length of open reading frame of transcript is 912 mer and translated to a 304 residues protein referred as c-Crk-II. (atlasgeneticsoncology.org)
  • this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. (rcsb.org)
  • Schneider GB, Gilmore AP, Lohse DL, Romer LH, Burridge K. Microinjection of protein tyrosine phosphatases into fibroblasts disrupts focal adhesions and stress fibers. (umassmed.edu)
  • Protein tyrosine phosphatases take off. (pubmedcentralcanada.ca)
  • 1002 protein phosphatases? (pubmedcentralcanada.ca)
  • Substrate specificities of catalytic fragments of protein tyrosine phosphatases (HPTP beta, LAR, and CD45) toward phosphotyrosylpeptide substrates and thiophosphotyrosylated peptides as inhibitors. (pubmedcentralcanada.ca)
  • Comparison of the specificity of bacterially expressed cytoplasmic protein-tyrosine phosphatases SHP and SH-PTP2 towards synthetic phosphopeptide substrates. (pubmedcentralcanada.ca)
  • Desai CJ, Gindhart JG, Jr, Goldstein LS, Zinn K. Receptor tyrosine phosphatases are required for motor axon guidance in the Drosophila embryo. (pubmedcentralcanada.ca)
  • In the current work, we report that three protein tyrosine phosphatases, PTP-1B, SHP-2, and PTEN, are involved in Rb/E2F-associated apoptosis. (aacrjournals.org)
  • In this study, we used a neonatal rat ventricular myocyte (NRVM) model to determine the role of focal-adhesion kinase (FAK) in β 1 integrin mediated MAP kinase activation in response to mechanical stretch in presence and absence of Ang II receptor blockade (ATB). (pubmedcentralcanada.ca)
  • I n recent years it has become evident that integrin- mediated adhesion to extracellular matrix (ECM) 1 proteins is required for growth and survival of many cell types. (rupress.org)
  • The mechanism by which integrin-mediated ECM adhesion is able to prevent apoptosis is unclear and under intense investigation. (rupress.org)
  • Although PYK2 can be activated following integrin mediated adhesion, PYK2 is primarily activated in response to a variety of stimuli that increase intracellular calcium . (axonmedchem.com)
  • In vivo evaluation of hsp27 as an inhibitor of actin polymerization: hsp27 limits actin stress fiber and focal adhesion formation after heat shock. (umassmed.edu)
  • These results suggest that TAE226, a dual tyrosine kinase inhibitor for FAK and IGF-IR, could become a new remedy for Barrett's esophageal adenocarcinoma. (aacrjournals.org)
  • Duvelisib is an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma being investigated for the treatment of hematologic cancers, including chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma (iNHL) and T cell lymphomas. (corporate-ir.net)
  • 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)
  • A requirement for SFK function in G 1 -S progression after treatment with PDGF and EGF has been demonstrated in fibroblasts using microinjection of mutant Src proteins and treatment with a selective small molecule Src kinase inhibitor, SU6656 ( 14 - 16 ). (aacrjournals.org)
  • Duvelisib is a first-in-class oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma that is currently being developed for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL). (biospace.com)
  • Defactinib is an oral small molecule inhibitor of focal adhesion kinase (FAK) and is currently being evaluated in combination with immunotherapeutic agents for the treatment of various cancers including pancreatic, ovarian and non-small cell lung cancer, and mesothelioma. (biospace.com)
  • Both of the amitriptyline-induced ERK activation and GDNF mRNA expression were blocked by genistein, a general protein tyrosine kinase (PTK) inhibitor. (aspetjournals.org)
  • Inhibition of dynamin prevents migration of cells with a focal adhesion phenotype. (nih.gov)
  • Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. (nih.gov)
  • Inhibition of focal adhesion kinase with her-2 targeted antibody pertuzumab (Omnitarg, 2C4) in breast cancer cells. (ebscohost.com)
  • In contrast, inhibition of MEK and PI3-kinase did not affect osteopontin-induced NF-κB activation. (rupress.org)
  • Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. (nih.gov)
  • In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 ( NF2 ) tumor suppressor gene product, Merlin. (sciencemag.org)
  • Most tyrosine kinases have an associated protein tyrosine phosphatase, which removes the phosphate group. (wikipedia.org)
  • Identification of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST. (pubmedcentralcanada.ca)
  • PTP-PEST is a ubiquitously expressed, cytosolic, mammalian protein tyrosine phosphatase (PTP) which exhibits high specific activity in vitro. (pubmedcentralcanada.ca)
  • Crystal structure of human protein tyrosine phosphatase 1B. (pubmedcentralcanada.ca)
  • Purification and crystallization of the catalytic domain of human protein tyrosine phosphatase 1B expressed in Escherichia coli. (pubmedcentralcanada.ca)
  • Charest A, Wagner J, Shen SH, Tremblay ML. Murine protein tyrosine phosphatase-PEST, a stable cytosolic protein tyrosine phosphatase. (pubmedcentralcanada.ca)
  • den Hertog J, Pals CE, Jonk LJ, Kruijer W. Differential expression of a novel murine non-receptor protein tyrosine phosphatase during differentiation of P19 embryonal carcinoma cells. (pubmedcentralcanada.ca)
  • Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis. (pubmedcentralcanada.ca)
  • Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation. (pubmedcentralcanada.ca)
  • The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. (pubmedcentralcanada.ca)
  • It is characterized by inactivation of focal adhesion kinase (FAK) through dephosphorylation by protein tyrosine phosphatase(s). (aacrjournals.org)
  • The predicted PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. (sciencemag.org)
  • Here we report that the netrin receptor DCC (deleted in colorectal cancer) interacts with the focal adhesion kinase (FAK), a kinase implicated in regulating cell adhesion and migration. (nih.gov)
  • During disassembly, dynamin interacts with FAK and colocalizes with focal adhesions. (nih.gov)
  • 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)
  • These include the Src family members, Lck and Fyn, which constitutively associate with the TCR/CD3 and the CD4/CD8 coreceptors, respectively, and Zap70, a cytosolic PTK that is recruited to the activated TCR and interacts with its tyrosine-phosphorylated receptor subunits ( 6 , 7 ). (jimmunol.org)
  • Interacts with EPHA1 (kinase activity-dependent). (rcsb.org)
  • Moreover, it stimulates the E-cadherin regulator Hakai, interacts with and phosphorylates the novel podosome-linked adaptor protein Fish, and progressively phosphorylates the gap junction component connexion 43. (biologists.org)
  • also contributes to the transduction of signals downstream receptor tyrosine kinases (RTKs). (lookformedical.com)
  • Stimulation by receptor tyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. (uniprot.org)
  • It is believed that integrin-dependent autophosphorylation of FAK recruits and activates Src family kinases, which in turn trigger downstream signaling events. (pnas.org)
  • Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. (wikipathways.org)
  • When Src-transformed MDCK cells are surrounded by normal MDCK cells, myosin-II and focal adhesion kinase (FAK are activated in Src cells, which further activate downstream mitogen-activated protein kinase (MAPK. (zfin.org)
  • The major downstream effectors of RAS are RAFs (ARAF, BRAF, and CRAF), phosphoinositide 3-kinase (PI3K), and the Ral guanine exchange factors (RalGEF). (aacrjournals.org)
  • TANK-binding kinase 1 (TBK1) is an atypical IκB kinase family member that acts downstream of RalGEFs. (aacrjournals.org)
  • Immunostaining of BALB/c 3T3 fibroblasts revealed that FadK is concentrated in focal adhesions. (pnas.org)
  • The tyrosine kinase pp125FAK, by virtue of its focal adhesion localisation in fibroblasts, represents a prime candidate to perform this function. (biologists.org)
  • We investigated the development of F-actin stress fibres and focal adhesions in MASMC in response to adherence to fibronectin, conditions shown to promote cytoskeletal reorganisation in fibroblasts. (biologists.org)
  • Adherence to fibronectin has been reported to activate pp125FAK tyrosine kinase in fibroblasts, leading to the proposal that pp125FAK plays a critical role in focal adhesion formation. (biologists.org)
  • Fibroblasts - a type of cell that synthesizes the extracellular matrix and collagen and is involved in wound healing - that have been transformed by the polyomavirus possess higher tyrosine activity in the cellular matrix. (wikipedia.org)
  • Focal adhesion kinase (FAK or pp125 FAK ) was first identified as a v- src substrate in chicken embryo fibroblasts ( 1 ). (pnas.org)
  • Fibroblasts maintained in the absence of serum have stable adhesions within the rear of the cell and exhibit reduced trailing-edge retraction resulting in an elongated cell phenotype. (biologists.org)
  • We observed that maintaining fibroblasts in the absence of serum results in stabilization of adhesions within the rear of the cell, and significantly reduced trailing-edge retraction resulting in an elongated cell phenotype. (biologists.org)
  • The developmental defect observed in FAK-deficient mice may be associated with impairment of cell migration and enhancement of cell adhesion, as suggested by studies with FAK-/- fibroblasts (10). (scielo.br)
  • Protein and mRNA levels of several FA constituents regulated by the myocardin-related transcription factor (MRTF)-serum response factor (SRF) transcription factor complex were reduced in WIP −/− fibroblasts. (asm.org)
  • This protein localizes to both the cell nucleus and the cell periphery and is differently localized in fibroblasts and epithelial cells. (novusbio.com)
  • 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)
  • This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. (nih.gov)
  • Involved in calcium induced regulation of ion channel and activation of the map kinase signaling pathway. (hmdb.ca)
  • Ishida, K., Nagahara, H. and Kogiso, T. (2003) Cell adhesion aside from integrin system can abrogate anoikis in rat liver cells by down-regulation of FasL expression, not by activation of PI-3K/Akt and ERK signaling pathway. (scirp.org)
  • S. Akakura and I. H. Gelman provide insight into the regulation of AKAP12 and how it contributes to cell adhesion. (hindawi.com)
  • Changes in its DNA sequence transform it into an oncogene that leads to the formation of a different protein with implications for normal cell regulation. (wikipedia.org)
  • Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. (wikipathways.org)
  • Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. (wikipathways.org)
  • Focal adhesion kinase (FAK), guanine nucleotide exchange factors (GEF) for Rho and the Rho effector Rho kinase II (ROCKII) are crucial for the regulation of adhesion movement and trailing-edge retraction. (biologists.org)
  • GTRAP48 (rat)] in the regulation of adhesion movement, trailing-edge retraction and cell-shape change. (biologists.org)
  • Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling. (ebscohost.com)
  • 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)
  • 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)
  • In mouse NIH 3T3 cells transfected with wild-type ERα, phosphorylation of the kinase Akt was evident within 5 min of E 2 treatment, but such regulation of Akt was diminished in cells expressing a mutant form of ERα in which the site of methylation was modified to prevent methylation. (sciencemag.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)
  • These results strongly suggest that hyaluronate-CD44 signaling may play a role in tumor invasion and proliferation by activation of p125(FAK) and MAP kinase in human glioma cells. (spandidos-publications.com)
  • Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. (biomedsearch.com)
  • Importantly, microglia that are in direct contact with senile plaques exhibit high levels of tyrosine-phosphorylated proteins ( Wood and Zinsmeister, 1991 ), suggesting sustained activation of intracellular signaling processes. (jneurosci.org)
  • RRSP blocks RAS-MAPK kinase signaling by cleaving Ras and Rap1 within the switch I region between Y32 and D33. (bireme.br)
  • In turn, this mechanism impairs the activation of a major inside-out signaling pathway that triggers the conformational activation of integrin and, consequently, cell adhesion, migration, in vitro endothelial tube formation, and spheroid sprouting. (bireme.br)
  • Because p125 focal adhesion kinase (FAK) is a transducer in the b1-integrin signaling pathway, it is essential to cell adhesion and it is overexpressed in metastatic breast cancer, we hypothesized that attenuation of FAK might enhance the sensitivity of breast cancer cells to camptothecins. (scielo.org.ar)
  • Focal adhesion kinase (FAK), a transducer in the b1-integrin signaling pathway reported to be essential to intercellular adhesion (Maung et al . (scielo.org.ar)
  • 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)
  • These protein platforms recruit adaptor proteins and lead to the activation of complex network of signaling cascades that regulate basic cellular functions [ 16 , 36 ]. (hindawi.com)
  • These new adhesions can either disassemble, allowing cells to migrate, or continue to mature by recruiting signaling and structural proteins to these sites. (hindawi.com)
  • The dynamics and composition of adhesions are controlled by signaling networks that function to integrate molecular signals from outside and within cells. (hindawi.com)
  • A-Kinase-Anchoring Proteins (AKAP) are emerging as pivotal scaffolding proteins that bring together key signaling molecules to modulate cell migration. (hindawi.com)
  • They highlight critical tyrosine kinases and signaling proteins that regulate the assembly and function of these adhesive structures. (hindawi.com)
  • Focal adhesion kinase (Fak) has been implicated as a signaling molecule involved in the early response of cardiac myocytes to mechanical stress. (ahajournals.org)
  • FAK signaling was disrupted by infecting NRVM with adenovirus expressing FAK-related non-kinase (FRNK). (pubmedcentralcanada.ca)
  • HE4 gene interference downregulated the expression of MAPK and the FOCAL adhesion signaling pathway-associated molecules MKNK2 and LAMB2, and HE4 protein supplementation reversed this effect. (nih.gov)
  • Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neuronal signaling in development and normal cell physiology. (wikipedia.org)
  • Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. (wikipedia.org)
  • Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. (rcsb.org)
  • The combined findings illustrated the crucial role for a proline-rich tyrosine kinase 2-signaling complex in the endothelial response to salt intake. (ahajournals.org)
  • 22,25-27 Binding to Pyk2 activates c-Src and PI3-kinase, and this signaling complex participates in a variety of intracellular processes. (ahajournals.org)
  • Structure of signaling adaptor protein CrkII. (atlasgeneticsoncology.org)
  • Signaling adaptor protein which links tyrosine kinases and small G proteins. (atlasgeneticsoncology.org)
  • Promotes activation of MAPK1 /ERK2, MAPK3 /ERK1 and the MAP kinase signaling cascade. (rcsb.org)
  • Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2 /FAK1 phosphorylation and signaling. (rcsb.org)
  • By coordinating adhesion and cytoskeletal dynamics with survival and growth signaling, FAK and Pyk2 represent molecular therapeutic targets in cancer cells as malignant cells often exhibit defects in these processes. (axonmedchem.com)
  • Defective wound repair after CD47 loss is linked to decreased epithelial β1 integrin and focal adhesion signaling, as well as reduced thrombospondin-1 and TGF-β1. (nature.com)
  • 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)
  • 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)
  • 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)
  • HEF1 is a multifunctional protein involved in integrin-based signaling that affects cell motility, growth, apoptosis and oncogenic transformation. (acris-antibodies.com)
  • p53 signaling and cell cycle checkpoints were regulated by DOX while ErbB/PI3K-Akt, integrin and focal adhesion signaling were regulated by RM upon combination. (mdpi.com)
  • Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlin-negative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. (sciencemag.org)
  • MR-1 modulates proliferation and migration of human hepatoma HepG2 cells through myosin light chains-2 (MLC2)/focal adhesion kinase (FAK)/Akt signaling pathway. (umassmed.edu)
  • Arginine methylation of estrogen receptor alpha promotes its interaction with cytoplasmic signaling proteins. (sciencemag.org)
  • Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. (wikipedia.org)
  • Since overnight cultures of MASMC exhibited elevated pp125FAK tyrosine kinase activity, we investigated whether these cells deposit their own combination of extracellular matrix (ECM) molecules and/or secrete factors into their conditioned medium which are capable of activating pp125FAK tyrosine kinase. (biologists.org)
  • Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. (hindawi.com)
  • Adhesions are sites of contact between cells (cell-cell) and between cells and the extracellular matrix (cell-ECM) that are essential for numerous biological processes such as embryogenesis, wound healing, and the immune response. (hindawi.com)
  • Heparan sulfate proteoglycans (HSPGs) are constituents of the extracellular matrix, and through their heparan sulfate chains and protein core, modulate multiple events that occur during the metastatic cascade. (frontiersin.org)
  • This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. (sigmaaldrich.com)
  • 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)
  • This special issue focuses on the molecular signals that regulate adhesion dynamics with an emphasis on cell-ECM adhesions. (hindawi.com)
  • By definition as a proto-oncogene, Fyn codes for proteins that help regulate cell growth. (wikipedia.org)
  • Crk has been reported to bind to NS1 protein of influenza virus type H5N1, CagA protein of Helicobacter pylori, and also known to regulate the infection of Pseudomonas aeruginosa and Shigella flexneri. (atlasgeneticsoncology.org)
  • These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions. (sciencemag.org)
  • In other studies, Agrin was found to activate Yes- Associated Protein (YAP) to regulate a variety of cellular processes including cell proliferation, differentiation and migration, which can seriously affect repair of skin tissue damage [ 3 , 9 ]. (alliedacademies.org)
  • Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION. (umassmed.edu)
  • The arginine methyltransferase PRMT1 (protein arginine methyltransferase 1) is known to associate with Erα and to regulate its transcriptional activity. (sciencemag.org)
  • Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells. (nih.gov)
  • The objective of the present study was to identify human epididymis protein 4 (HE4) interacting proteins and explore the mechanisms underlying their effect on ovarian cancer cell invasion and metastasis. (nih.gov)
  • Integrin clusters in macromolecular complexes, ligand occupancy, and tyrosine phosphorylation are the key events that result in diverse processes such as cell migration and differentiation, tissue remodelling, cell proliferation, angiogenesis, and tumor cell invasion and metastasis (3,6). (scielo.br)
  • Degradation and Dephosphorylation of Focal Adhesion Kinase During Okadaic Acid-Induced Apoptosis in Human Neuroblastoma Cells. (ebscohost.com)
  • Focal adhesion kinase (FAK) prevents apoptosis in many cell types. (ebscohost.com)
  • 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)
  • Focal adhesion kinase (FAK) has been implicated in cellular processes that control cell adhesion, migration, cell cycle progression, and apoptosis. (semanticscholar.org)
  • The Cas family of docking proteins have been the subject of intense research because of their role in cell motility, growth, apoptosis and oncogenic transformation. (acris-antibodies.com)
  • Cellular growth and reproduction may rely to some degree on tyrosine kinase. (wikipedia.org)
  • Furthermore, tyrosine kinase activity has been determined to be correlated to cellular transformation. (wikipedia.org)
  • It has also been demonstrated that phosphorylation of a middle-T antigen on tyrosine is also associated with cell transformation, a change that is similar to cellular growth or reproduction. (wikipedia.org)
  • A protein tyrosine kinase called pp125 is likely at hand in the influence of cellular focal adhesions, as indicated by an immunofluorescent localization of the said kinase. (wikipedia.org)
  • Among the scientific community, pp125 is also referred to as FAK (focal adhesion kinase), due to its aforementioned presence in cellular focal adhesions. (wikipedia.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)
  • Focal adhesion formation and turnover has been used as a model system for understanding the mechanisms of cellular adhesion. (hindawi.com)
  • The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. (reactome.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)
  • 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)
  • Knockdown of Psoriasin in HaCaT cells was performed using anti‑Psoriasin ribozyme transgenes and the effect on growth, adhesion and migration of keratinocytes was subsequently determined using in vitro cellular functional assays. (spandidos-publications.com)
  • 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)
  • 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)
  • Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. (uniprot.org)
  • When esophageal adenocarcinoma cells were treated with TAE226, cell proliferation and migration were greatly inhibited with an apparent structural change of actin fiber and a loss of cell adhesion. (aacrjournals.org)
  • 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)
  • 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)
  • Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. (bireme.br)
  • 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)
  • 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)
  • Indeed, this dynamic nature of adhesions within localized regions of cells is critical for many complex processes such as cell migration. (hindawi.com)
  • They show that CNF1 and CNF γ increase cell-matrix adhesion, resulting in reduced migration. (hindawi.com)
  • A key step in cell migration is the dynamic formation and disassembly of adhesions at the front and the concomitant movement and release of adhesions in the rear of the cell. (biologists.org)
  • We identified AKT, p130CAS and focal adhesion kinase (FAK) as novel PTK6 substrates and demonstrated their roles in promoting cell proliferation, migration and resistance to anoikis. (wiley.com)
  • 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)
  • YopH tyrosine dephosphorylates host cell proteins, such as p130Cas and focal adhesion kinase FAK ( 2 ). (jimmunol.org)
  • most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2 /FAK1, rather than by PTK2 /FAK1 itself. (rcsb.org)
  • PTK2 (AAH28733, 355 a.a. ~ 490 a.a) partial recombinant protein with GST tag. (sigmaaldrich.com)
  • FadK is phosphorylated on tyrosine in growing cultures of BALB/c 3T3 cells but contains little or no phosphotyrosine in cells detached by trypsinization. (pnas.org)
  • The tyrosine-phosphorylated state is regained within minutes when the cells are replated onto fibronectin. (pnas.org)
  • The localization of PKD within cells is mediated by interaction with different lipid or protein binding partners. (elsevier.com)
  • Treatment of glioma cells with hyaluronate activated rapid and transient tyrosine phosphorylation of several proteins including p125(FAK), while neuroblastoma cells that express no detectable CD44 had no response to the treatment. (spandidos-publications.com)
  • During the early stages of adhesion, FAK expression in FAK-null cells enhances integrin activation to promote integrin binding and, hence, the adhesion strengthening rate. (biomedsearch.com)
  • one in which fibronectin promotes cytoskeletal reorganisation in the absence of pp125FAK tyrosine kinase activity and the other in which cells adhering to MASMC-ECM display elevated pp125FAK tyrosine kinase activity in association with an impaired ability to promote F-actin stress fibre and focal adhesion formation. (biologists.org)
  • 1994 ). The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated with increased tyrosine phosphorylation and the recruitment of both pp125FAKand protein kinase C-to focal adhesions. (biologists.org)
  • In addition, whereas FAK-expressing cells responded to exerted forces by reorienting their movements and forming prominent focal adhesions, FAK-null cells failed to show such responses. (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)
  • 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)
  • In this study, we pursued the possibility that FAK is involved in focal adhesion-mediated responses of cells to physical signals. (pnas.org)
  • Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. (hindawi.com)
  • In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. (hindawi.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)
  • Adhesions are dynamic structures whose molecular composition and structure can undergo rapid changes to allow cells to respond to external signals [ 1 , 4 ]. (hindawi.com)
  • Adherens junctions are cell-cell adhesion sites that are important for the establishment and maintenance of apico-basal polarity of epithelial cells. (hindawi.com)
  • 8,9 In addition, Fak, a primary integrin effector that is known to play a key role in the responses of cells to mechanical stimuli through focal adhesion sites, 10-12 is rapidly activated by mechanical stimuli in cultured neonatal rat ventricular myocytes (NRVMs) 13,14 and in overloaded myocardium of adult animals. (ahajournals.org)
  • The scratch test, the Transwell assay and animal experiments were used to assess the invasive and metastatic abilities of ovarian cancer cells before and after transfection and HE4 protein treatment. (nih.gov)
  • Using primary cultured Sertoli cells as an in vitro model that mimics the BTB in vivo both functionally and ultrastructurally, effects of FAK phosphorylation on BTB function were studied by expressing nonphosphorylatable and phosphomimetic mutants, with tyrosine replaced by phenylalanine (F) and glutamate (E), respectively. (popcouncil.org)
  • We report here that Shigella invasion of epithelial cells requires rho activity, a ras-related GTP-binding protein. (rupress.org)
  • Protrusion of the leading edge and the establishment of new peripheral adhesions coupled with the maintenance of stable attachments at the cell rear create the typical asymmetrical profile of a migrating cells with a broad lamellipodia (front) and narrow long trailing edge (rear) ( Regen and Horwitz, 1992 ). (biologists.org)
  • Using a panel of highly selective and structurally diverse Src inhibitors, we found that phosphorylation of signal transducer and activator of transcription 3 [STAT3 (Y705)] and focal adhesion kinase [FAK (Y861)] was SFK dependent in cultured human colon, breast, lung, and ovarian tumor cells. (aacrjournals.org)
  • Dynamic Change in Morphology and Traction Forces at Focal Adhesions in Cultured Vascular Smooth Muscle Cells During Contraction. (ebscohost.com)
  • In order to study how cells change their traction forces at focal adhesions (FAs) following cell contraction, we observed the dynamic changes in traction forces at FAs, the morphology of FAs, and actin stress fibers (SFs) anchoring FAs in cultured porcine aortic smooth muscle cells (SMCs) during. (ebscohost.com)
  • WIP −/− cells had defective focal adhesion (FA), stress fiber assembly, and adherence to substrates, functions that were restored by transduction of wild-type WIP. (asm.org)
  • The most important initiator of actin assembly in cells is the Arp2-Arp3 (Arp2/3) complex, a ubiquitously expressed heteropolymer of seven proteins. (asm.org)
  • In unstimulated cells, most of the NF-κB is localized in the cytoplasm in complex with an inhibitory protein, IκB( Baldwin, 1996 ). (rupress.org)
  • Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. (nih.gov)
  • 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)
  • Depletion of PRMT1 from cells by treating them with siRNA inhibited the formation of the protein complex. (sciencemag.org)
  • This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK, and the SH2 domain of GRB2. (nih.gov)
  • The enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine-specific, and tyrosine-specific (the subject of this article). (wikipedia.org)
  • However, a difference in the processing efficiency of Ras switch I in the context of Ras, RalA, or RhoA indicates that protein regions outside Ras switch I also contribute to efficient RRSP substrate recognition. (bireme.br)
  • In conclusion, this work demonstrates that the GTPase recognition of RRSP is independent of the nucleotide state and is mainly driven by the Ras and Rap1 switch I loop and also influenced by additional protein-protein interactions, increasing the substrate specificity of RRSP. (bireme.br)
  • 18,19 In particular, NOS3 can serve as a substrate for protein kinase B (Akt), which promotes serine phosphorylation at residue 1176 in the carboxyl terminal portion of NOS3 and increases NOS3 sensitivity to calcium/calmodulin and enzyme activity. (ahajournals.org)
  • Phosphorylation of these dual tyrosines leads to the conformational changes in the JAK protein to facilitate binding of substrate. (wikipedia.org)
  • HEF1, also known as Enhancer of filamentation 1, CRKassociated substrate-related protein, CAS-L, CasL, p105 and Neural precursor cell expressed developmentally down-regulated 9 is the product of the NEDD9 (CASGL) gene. (novusbio.com)
  • Instead, total internal reflection fluorescence microscopy demonstrated mislocalization of actin nucleation protein Arp2 microclusters, but not those containing the adaptor proteins SLP-76 and WASp, or the actin nucleation protein ARPC3, which are necessary for TCR-induced actin rearrangement. (sciencemag.org)
  • Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. (rcsb.org)
  • Recent studies show that dietary salt intake activates proline-rich tyrosine kinase 2 (Pyk2). (ahajournals.org)
  • Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. (reactome.org)
  • Crk activates Fak and transmit signals to PI3 kinase. (atlasgeneticsoncology.org)
  • With the example of PKD2, we here show that phosphorylation events can also contribute to localization of subcellular pools of this kinase. (elsevier.com)
  • 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)
  • Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, displays phosphorylation-dependent localization in the seminiferous epithelium of adult rat testes. (popcouncil.org)
  • The carboxy-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions. (rcsb.org)
  • Focal adhesions are macromolecular structures that function in the transmission of mechanical force and regulatory signals. (wikipedia.org)
  • 6-10 However, the mechanisms by which these structures and proteins detect physical forces and initiate biochemical signals are yet unclear. (ahajournals.org)
  • May function in transmitting growth control signals between focal adhesions at the cell periphery and the mitotic spindle in response to adhesion or growth factor signals initiating cell proliferation. (rcsb.org)
  • The nature of the signals that promote dissociation/degradation of the adhesions in the trailing edge is poorly understood. (biologists.org)
  • Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. (wikipedia.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)
  • Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded by the FYN gene. (wikipedia.org)
  • Among these was the S100 calcium-binding protein A7 gene (Psoriasin), which expresses protein products that have been proposed to be associated with keratinocyte differentiation. (spandidos-publications.com)
  • The protein encoded by this gene binds GTP and is a member of the small GTPase superfamily. (genecards.org)
  • RHOD (Ras Homolog Family Member D) is a Protein Coding gene. (genecards.org)
  • Focal adhesion kinase (FAK) is an important cancer target because FAK gene amplification and protein overexpression have been demonstrated in a wide range of malignancies ( 1 ). (sciencemag.org)
  • C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene. (wikipedia.org)
  • The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. (wikipedia.org)
  • Fyn is a member of the Src-family of kinases (SFK), the first proto-oncogene to be identified. (wikipedia.org)
  • 11,12 Focal adhesion kinase (Fak), a primary integrin effector at focal adhesion sites, 15-17 is rapidly activated by mechanical stimuli in cultured neonatal rat ventricular myocytes 18-20 and in overloaded myocardium of adult animals. (ahajournals.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)
  • 10 ) revealed that YopP/YopJ binds and inactivates members of the MAPK kinase superfamily, which function as upstream MAPK activators. (jimmunol.org)
  • Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. (asm.org)
  • pp125FAK and p41/p43FRNK were localized to focal adhesions, suggesting that pp125FAK is directed to the focal adhesions by sequences within its C-terminal domain. (asm.org)
  • We also show that the fibronectin-dependent increase in tyrosine phosphorylation of pp125FAK is accompanied by a concomitant posttranslational modification of p41FRNK. (asm.org)
  • We have shown that vinculin, pp125FAK and tyrosine-phosphorylated proteins are localised in focal adhesions during this time period. (biologists.org)
  • MASMC, under these culture conditions exhibit elevated pp125FAK tyrosine kinase activity, as measured by an increased autophosphorylation potential. (biologists.org)
  • Within 30 minutes, MASMC exhibited well-developed F-actin stress fibres and prominent focal adhesions which immunostained intensely for vinculin, pp125FAK and phosphotyrosine. (biologists.org)
  • Anti-phosphotyrosine immunoblotting and in vitro kinase assays of MASMC lysates have revealed that, under conditions which promote focal adhesion formation, pp125FAK remains inactive. (biologists.org)
  • Our results indicate that MASMC-elaborated ECM, but not their conditioned medium, supported pp125FAK tyrosine kinase activation. (biologists.org)
  • These results indicate that in MASMC, pp125FAK tyrosine kinase activity is not involved in F-actin stress fibre assembly and focal adhesion formation. (biologists.org)
  • 1994 ). Stable association of pp60srcand pp59fynwith the focal adhesion-associated protein tyrosine kinase, pp125FAK. (biologists.org)
  • Kinase (pp125FAK) reacts with a 125 kDa. (acronymattic.com)
  • Forms complexes in vivo with related adhesion focal tyrosine kinase (RAFTK), adapter protein CRKL and LYN kinase. (rcsb.org)
  • 21 Pyk2 (also designated FAK2, CAK-ß, CADTK, or RAFTK) is a member of the focal adhesion protein tyrosine kinase family. (ahajournals.org)
  • The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. (cellsignal.com)
  • 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)
  • A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16. (nih.gov)
  • In addition to duvelisib, Verastem also holds worldwide rights to the tumor microenvironment-targeting focal adhesion kinase (FAK) inhibitors defactinib (VS-6063) and VS-4718. (corporate-ir.net)
  • Auvinen M, Paasinen-Sohns A, Hirai H, Andersson LC, Hölttä E. Ornithine decarboxylase- and ras-induced cell transformations: reversal by protein tyrosine kinase inhibitors and role of pp130CAS. (pubmedcentralcanada.ca)
  • Here, we found that amitriptyline, a tricyclic antidepressant, increased both GDNF mRNA expression and release, which were selectively and completely inhibited by mitogen-activated protein kinase kinase inhibitors. (aspetjournals.org)
  • Background Focal adhesion Kinase (FAK) is a nonreceptor proteins tyrosine kinase that is overexpressed in tumors and plays a significant role in tumor survival and PD318088 metastasis. (healthcarecoremeasures.com)
  • The Src family kinases (SFKs) Src and Yes are believed to play critical roles in tumor growth, angiogenesis, invasion, and dissemination. (aacrjournals.org)
  • Crk was originally isolated as avian retrovirus (CT10, chicken tumor No. 10) encoding oncoprotein as v-Crk (viral Crk, CT10 regulator of kinase). (atlasgeneticsoncology.org)
  • In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. (hindawi.com)
  • 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)
  • Here we show that netrin-1 induces tyrosine phosphorylation of proteins including focal adhesion kinase (FAK) and the Src family kinase Fyn. (ebscohost.com)
  • 1992) pp125 FAK, a structurally distinctive proteintyrosine kinase associated with focal adhesions. (scirp.org)
  • Here, we develop a model system of focal adhesion disassembly based on the finding that microtubule regrowth after nocodazole washout induces disassembly of focal adhesions, and that this disassembly occurs independently of Rho and Rac, but depends on focal adhesion kinase (FAK) and dynamin. (nih.gov)
  • Imaging studies implicate microtubule targeting of focal adhesions in focal adhesion disassembly, although the molecular mechanism is unknown. (nih.gov)
  • Here we identify the molecular events evoked by the HIV coat protein gp120 that facilitate the intraneuronal accumulation of A? (jove.com)
  • We quantified the abundance of complexes in the cytoplasm among the MAPKs Ste11, Ste7, Fus3 and the scaffold protein Ste5 in yeast pheromone. (ebscohost.com)
  • Focal adhesion kinase modulates cell adhesion strengthening via integrin activation. (biomedsearch.com)
  • 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. (nih.gov)
  • Its activation is highly correlated with the stimulation of c-Jun N-terminal kinase activity. (hmdb.ca)
  • Activation of NF-κB by osteopontin depended on the small GTP-binding protein Ras and the tyrosine kinase Src, since NF-κB reporter activity was inhibited by Ras and Src dominant-negative mutants. (rupress.org)
  • Journal Article] Activation of MTK1/MEKK4 by GADD45 through induced N-C dissociation and dimerization-mediated trans autophosphorylation of the MTK1 kinase domain. (nii.ac.jp)
  • JH1 is the kinase domain important for the enzymatic activity of the JAK and contains typical features of a tyrosine kinase such as conserved tyrosines necessary for JAK activation (e.g. (wikipedia.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 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)
  • Fifteen to 20% of patients with melanoma have mutations in NRAS , most frequently Q61R/K/L that trap the protein in a GTP-bound state, leading to its constitutive activation ( 5, 6 ). (aacrjournals.org)
  • Here we report the isolation of cDNAs encoding the C-terminal, noncatalytic domain of the FAK kinase, termed FRNK (FAK-related nonkinase). (asm.org)
  • Our results demonstrate that the protein-chromophore interactions responsible for blue-shifting the absorbance and emission maxima of mTFP1 operate independently of the chromophore structure. (biomedcentral.com)