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.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
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.
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.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The portion of an interactive computer program that issues messages to and receives commands from a user.
Sequential operating programs and data which instruct the functioning of a digital computer.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Male germ cells derived from the haploid secondary SPERMATOCYTES. Without further division, spermatids undergo structural changes and give rise to SPERMATOZOA.
The epithelium lining the seminiferous tubules composed of primary male germ cells (SPERMATOGONIA) and supporting SERTOLI CELLS. As SPERMATOGENESIS proceeds, the developing germ cells migrate toward the lumen. The adluminal compartment, the inner two thirds of the tubules, contains SPERMATOCYTES and the more advanced germ cells.
The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.
The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA.
Supporting cells projecting inward from the basement membrane of SEMINIFEROUS TUBULES. They surround and nourish the developing male germ cells and secrete ANDROGEN-BINDING PROTEIN and hormones such as ANTI-MULLERIAN HORMONE. The tight junctions of Sertoli cells with the SPERMATOGONIA and SPERMATOCYTES provide a BLOOD-TESTIS BARRIER.
A specialized barrier, in the TESTIS, between the interstitial BLOOD compartment and the adluminal compartment of the SEMINIFEROUS TUBULES. The barrier is formed by layers of cells from the VASCULAR ENDOTHELIUM of the capillary BLOOD VESSELS, to the SEMINIFEROUS EPITHELIUM of the seminiferous tubules. TIGHT JUNCTIONS form between adjacent SERTOLI CELLS, as well as between the ENDOTHELIAL CELLS.
Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
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.
A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182)
Four carbon unsaturated hydrocarbons containing two double bonds.
Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.
A system of NEURONS that has the specialized function to produce and secrete HORMONES, and that constitutes, in whole or in part, an ENDOCRINE SYSTEM or organ.
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
A plant genus of the family APIACEAE. Members contain osthol.
A cell line derived from cultured tumor cells.
A large plant family in the order Apiales, also known as Umbelliferae. Most are aromatic herbs with alternate, feather-divided leaves that are sheathed at the base. The flowers often form a conspicuous flat-topped umbel. Each small individual flower is usually bisexual, with five sepals, five petals, and an enlarged disk at the base of the style. The fruits are ridged and are composed of two parts that split open at maturity.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)
Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.
A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.
Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.
Constriction of arteries in the SKULL due to sudden, sharp, and often persistent smooth muscle contraction in blood vessels. Intracranial vasospasm results in reduced vessel lumen caliber, restricted blood flow to the brain, and BRAIN ISCHEMIA that may lead to hypoxic-ischemic brain injury (HYPOXIA-ISCHEMIA, BRAIN).
Neuropilins are 140-kDa vertebrate cell surface receptors that bind neuronal guidance molecules during neural development and axonal outgrowth, and modulate VEGF-mediated angiogenesis. NEUROPILIN-1 and NEUROPILIN-2 differ in their binding specificities, and are distributed complementarily in regions of the developing nervous system. Neuropilins are receptors for secreted CLASS 3 SEMAPHORINS as well as for vascular endothelial growth factors, and may form hetero- or homodimers. They may also interact synergistically with plexins and with VEGF RECEPTORS to form receptor complexes with distinct affinities and specificities. Neuropilin binding specificity is determined by CUB and coagulation-factor-like domains in the extracellular portion of the molecule, while a MAM domain is essential for SIGNAL TRANSDUCTION.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
Transmembrane receptor for CLASS 3 SEMAPHORINS and several vascular endothelial growth factor isoforms. Neuropilin-2 functions either as a homodimer or as a heterodimer with NEUROPILIN-1. The binding affinity of neuropilin-2 varies for different class 3 semaphorin isoforms and is dependent on the composition of the dimer. The protein also forms receptor complexes with plexins and with VEGF RECEPTORS, which alters the binding characteristics of the receptor.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
A family of proteins that mediate axonal guidance. Semaphorins act as repulsive cues for neuronal GROWTH CONES and bind to receptors on their filopodia. At least 20 different molecules have been described and divided into eight classes based on domain organization and species of origin. Classes 1 and 2 are invertebrate, classes 3-7 are vertebrate, and class V are viral. Semaphorins may be secreted (classes 2, 3, and V), transmembrane (classes 1, 4, 5, and 6), or membrane-anchored (class 7). All semaphorins possess a common 500-amino acid extracellular domain which is critical for receptor binding and specificity, and is also found in plexins and scatter factor receptors. Their C termini are class-specific and may contain additional sequence motifs.

CD28 ligation induces tyrosine phosphorylation of Pyk2 but not Fak in Jurkat T cells. (1/1396)

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. (2/1396)

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. (3/1396)

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. (4/1396)

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)

Interactions between two cytoskeleton-associated tyrosine kinases: calcium-dependent tyrosine kinase and focal adhesion tyrosine kinase. (5/1396)

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)

Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal. (6/1396)

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)

Gastrin stimulates the formation of a p60Src/p125FAK complex upstream of the phosphatidylinositol 3-kinase signaling pathway. (7/1396)

The molecular events whereby gastrin occupancy of G/CCK(B) receptors leads to phosphatidylinositol (PI) 3-kinase activation have been examined. We report here that this peptide promotes the association between two non-receptor tyrosine kinases, p60Src and p125FAK, and elicits a parallel increase in tyrosine phosphorylation and activity of both kinases. Gastrin-induced PI 3-kinase activity was coprecipitated with p60Src and p125FAK and was inhibited by herbimycin A, the selective Src inhibitor PP-2 or cytochalasin D, which disrupts the actin cytoskeleton and prevents p125FAK activity. These results indicate, for the first time, that a p60Src/p125FAK complex acts upstream of the gastrin-stimulated PI 3-kinase pathway.  (+info)

Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization. (8/1396)

We have previously reported the identification of four autophosphorylation sites on the KDR VEGF receptor. Two of these sites (tyrosines 951 and 996) are located in the receptor's kinase insert domain, and two (tyrosines 1054 and 1059) are located in the catalytic domain. In order to clarify the functional significance of these sites, we made DNA constructs in which tyrosine codons were replaced with those for phenylalanine, and expressed the DNA constructs in 293 cells. VEGF binding to cells expressing the native receptor led to a rapid increase in receptor and PLC-gamma phosphorylation, and a slower increase in the phosphorylation of p125FAK and paxillin. VEGF binding to KDR(Y951F) and KDR(Y996F) expressing cells resulted in phosphorylation of all cellular substrates tested, although the level of PLCgamma phosphorylation was decreased for KDR(Y996F). The decreased level of PLCgamma phosphorylation was not because PLCgamma-containing SH2 domains bind to the Y996 autophosphorylation site. We conclude that there exists receptor autophosphorylation sites not previously identified which allow for signaling via PLCgamma, as well as p125FAK and paxillin. VEGF binding to cells expressing KDR mutated at both tyrosine's 1054 and 1059 activated receptor autophosphorylation but at a level which was only 10% of that seen for cells expressing native receptor. Tyrosine phosphorylation of cell signaling proteins was not observed in KDR(Y1054,1059) expressing cells. Utilizing an in vitro assay which directly measures receptor catalytic activity allowed us to determine that the tyrosine kinase activity of the native receptor was significantly greater than that for the double mutant. We conclude from this result that VEGF-induced autophosphorylation at tyrosines 1054 and 1059 is a required step for allowing maximal KDR kinase activity. Maximal rates of receptor kinase activity is required for VEGF-induced receptor internalization, as internalization was delayed in the KDR(Y1054,1059F) expressing cells when compared to cells expressing native receptor.  (+info)

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 ...
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.
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 ...
Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving as a junction between the extracellular matrix and actin cytoskeleton. Actin dynamics is known as a determinant step in insulin secretion. Additionally, FAK has been shown to regulate insulin signaling. To investigate the essential physiological role of FAK in pancreatic β-cells in vivo, we generated a transgenic mouse model using rat insulin promoter (RIP)-driven Cre-loxP recombination system to specifically delete FAK in pancreatic β-cells. These RIPcre+fakfl/fl mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell viability and proliferation resulting in decreased β-cell mass was observed in these mice, which was associated with attenuated insulin/Akt (also known as protein kinase B) and extracellular signal-related kinase 1/2 signaling and increased caspase 3 activation. FAK-deficient β-cells exhibited impaired insulin secretion with normal glucose sensing and preserved Ca2+ ...
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 ...
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 ...
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. ...
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
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 ...
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
TY - JOUR. T1 - Promotion of skeletal muscle differentiation by K252a with tyrosine phosphorylation of focal adhesion. T2 - A possible involvement of small GTPase Rho. AU - Lee, Kun Ho. AU - Lee, Seung Hye. AU - Kim, Daegun. AU - Rhee, Sangmyung. AU - Kim, Chungho. AU - Chung, Chin Ha. AU - Kwon, Hyockman. AU - Kang, Man Sik. PY - 1999/11/1. Y1 - 1999/11/1. N2 - K252a, a protein kinase inhibitor, acts as a neurotrophic factor in several neuronal cells. In this study we show that K252a enhanced the differentiation of C2C12 myoblasts as well as tyrosine phosphorylation of several focal adhesion-associated proteins including p130(Cas), focal adhesion kinase, and paxillin. The tyrosine phosphorylation of these proteins, reaching a maximum at 30 min after K252a treatment, closely correlated with the colocalization of these proteins in focal adhesion complexes and the coimmunoprecipitation of these proteins with p130(Cas). In addition, K252a stimulated longitudinal development of stress fiber-like ...
Title:Focal Adhesion Kinase in Ovarian Cancer: A Potential Therapeutic Target for Platinum and Taxane-Resistant Tumors. VOLUME: 19 ISSUE: 3. Author(s):Arkene Levy*, Khalid Alhazzani, Priya Dondapati, Ali Alaseem, Khadijah Cheema, Keerthi Thallapureddy, Paramjot Kaur, Saad Alobid and Appu Rathinavelu. Affiliation:College of Medical Sciences, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, Rumbaugh Goodwin ...
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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 ...
TY - JOUR. T1 - EPS8 facilitates cellular growth and motility of colon cancer cells by increasing the expression and activity of focal adhesion kinase. AU - Maa, Ming Chei. AU - Lee, Jenq Chang. AU - Chen, Yen Jen. AU - Chen, Yun Ju. AU - Lee, Yuch Ching. AU - Wang, Shan Tair. AU - Huang, Ching Chung. AU - Chow, Nan Haw. AU - Leu, Tzeng Horng. PY - 2007/7/6. Y1 - 2007/7/6. N2 - In an attempt to study the role of Eps8 in human carcinogenesis, we observe that ectopic overexpression of Eps8 in SW480 cells (low Eps8 expression) increases cell proliferation. By contrast, expressing eps8 small interference RNA in SW620 and WiDr cells (high Eps8 expression) reduces their proliferation rate. Interestingly, attenuation of Eps8 decreases Src Pi-Tyr-416, Shc Pi-Tyr-317, and serum-induced FAK Pi-Tyr-397 and Pi-Tyr-861. Remarkably, by virtue of mammalian target of rapamycin/STAT3 Pi-Ser-727, Eps8 modulates FAK expression required for cell proliferation. Within 62% of colorectal tumor specimens examined, ...
Data Availability StatementNot applicable Abstract Background While aberrant activation from the chromatin-remodeling SWI/SNF complexes continues to be connected with cancers development and advancement, the role of every subunit in tumor cells is described poorly. cancer tumor cells and sensitized tumor cells to anoikis. In response to lack of connection, SMARCE1 interacted with and potentiated transcriptional activity of HIF1A, leading to speedy PTK2 activation. Both HIF1A and PTK2 were indispensable for SMARCE1-mediated safety against anoikis by advertising activation of ERK and AKT pathways while suppressing the manifestation of pro-apoptotic BIM protein. Expression data analysis of a large cohort of human being breast tumors exposed that high manifestation of SMARCE1 or PTK2 is definitely associated with poor prognosis and tumor relapse, and PTK2 manifestation is definitely positively correlated with SMARCE1 manifestation in basal-like and luminal B subtypes of breast tumors. Conclusions ...
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Netrins are a family of secreted molecules that are important for axonal outgrowth and guidance in the developing nervous system. However, the signaling mechanisms that lie immediately downstream of netrin receptors remain poorly understood. Here we report that the netrin receptor DCC (deleted in co …
In this report, we provide several lines of evidence that p130Cas is a downstream mediator of FAK-promoted cell migration. First, a mutation of P712/715A in FAK abolished its ability to promote CHO cell migration (Fig. 3). The proline-rich region on FAK spanning amino acids 712-718 has been mapped as the primary binding site for p130Cas through its SH3 domain (Polte and Hanks, 1995; Harte et al., 1996), although a second proline-rich region (amino acids 875-884) can also mediate FAK binding to p130Cas (Harte et al., 1996; Polte and Hanks, 1997). In vivo coimmunoprecipitation experiments showed that FAK/ p130Cas association was reduced but not abolished by the P712/715A mutation (Fig. 6), indicating that the second proline-rich region on FAK may mediate some binding to p130Cas, as demonstrated previously (Harte et al., 1996; Polte and Hanks, 1997). However, binding of p130Cas to an alternative site clearly does not allow for FAK-promoted migration. It has also been suggested that p130Cas may ...
Advanced stages of epithelial carcinogenesis are linked to loss of intercellular adhesion, but it remains unclear how alterations in cell‐cell and cell‐matrix adhesions are coordinated to promote the early stages of cancer development. To address this, we used 3D tissue models that mimic human premalignant disease, and studied the impact of E‐cadherin suppression in early stage, epithelial tumor cells (HaCaT‐II‐4) on the expression and activity of Focal Adhesion Kinase (FAK) and Src kinase and on tumor cell motility and invasiveness. Suppression of E‐cadherin function triggered elevated expression of FAK, increased tyrosine phosphorylation of FAK and Src, and redirected these protein tyrosine kinases to a perinuclear distribution. Pharmacological inhibition of FAK or Src, by either Tyrphostin AG1007 or PP2, reduced their phosphorylation, and reversibly inhibited tumor cell motility in 2D, monolayer cultures. Decreased FAK or Src expression by lentivirus‐mediated shRNA restored ...
Cancer Therapeutics CRC Pty Ltd is developing small molecule focal adhesion kinase (FAK) inhibitors for the treatment of metastatic cancers. Focal adhesion
Introduction Weve shown previously that overexpression of constitutively dynamic Akt or activation of Akt due to constitutively dynamic Ras or individual epidermal development aspect receptor-2 (HER2) confers in breast cancers cells level of resistance to chemotherapy or radiotherapy. on phosphoinositide 3-kinase (PI3-K). An elevated baseline degree of Akt was within MCF7 cells treated with ionizing rays also. The cellular replies to doxorubicin-induced Akt phosphorylation had been potentiated following the appearance of Akt upstream activators including HER2, HER3 and focal adhesion kinase. Bottom line Used as well as our latest released outcomes displaying that constitutive Akt mediates level of resistance to radiotherapy or chemotherapy, our 443776-49-6 IC50 443776-49-6 IC50 present data claim that the doxorubicin-induced phosphorylation and activation of Akt might reveal a cellular protective mechanism of tumor cells to get over doxorubicin-induced cytotoxic results, which further works ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Ms. Kelsey Murrell was mentored by Dr. Richard Price and graduate co-mentor Josh Meisner(BME). Kelseys research goal was to determine the role of the signaling enzyme Focal Adhesion Kinase in macrophages, which are agents of the immune system that play a critical role in the expansion of existing blood vessels when blood flow through normal circulatory channels is blocked. Her work could lead to better understanding and treatment of peripheral artery disease ...
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 ...
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.
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 ...
Our studies point to several important roles for FAK in the progression of cancer in the TRAMP model. First, loss of FAK expression by targeted deletion in prostate epithelial cells did not alter the time to appearance or the frequency of well-differentiated adenocarcinoma, indicating that FAK expression is not necessary for the development of these of early intraepithelial lesions. In contrast, all neuroendocrine tumors expressed FAK and seemed to have escaped Cre-mediated recombination at both the FAK and the Rosa26-LacZ loci. These observations suggest a role for FAK function in progression to the more aggressive neuroendocrine tumors and a less important role in development of early in situ lesions. It is possible that the early progenitor cells that give rise to neuroendocrine tumors become transformed by expression of T-antigen but fail to express Cre, thus accounting for the observed expression of FAK and the lack of expression of β-galactosidase. To test this possibility, we used the ...
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 ...
Colon cancer cells show increased resistance to chemotherapeutic agents compared to breast cancer cells (28, 29), and the molecular mechanisms of this resistance are not fully known. While colon cancer cells express high levels of Src family kinases (30), the survival signal pathways associated with its expression are not known (31). In the present study, we have demonstrated that colon cancer cell lines have survival signals operative through both FAK and Src activities, suggesting that the combination of these signals may contribute to their resistance to apoptosis. Furthermore, these results have shown for the first time that combined dual Src and FAK inhibition is effective for inducing apoptosis in colon cancer cell lines.. Several studies have demonstrated up-regulation of FAK expression in colorectal cancer (11, 13, 14, 24, 25, 32), and it appears that colon cells up-regulate expression of FAK at early stages of tumorigenesis, even before carcinoma has been detected (11). Our previous ...
To decipher how cells crawl, researchers have knocked out a key signaling protein known as focal adhesion kinase (FAK), which relays messages from the cell surface. But the results of these knockout studies have been confused by the fact that a FAK paralogue gets up-regulated in these cells. Lim et al. now clear up the picture.. As a cell crawls along a surface, it temporarily attaches at sites called focal adhesions. FAK concentrates at focal adhesions and passes on signals from integrins that have latched onto molecules in the extracellular matrix. Fibroblasts missing FAK remain rounded up instead of flattening out on a surface and crawl sluggishly. Both of which might be expected if focal adhesions are impaired. However, FAK-lacking cells actually have an inordinate number of focal adhesions and have increased RhoA activity-a factor that spurs focal adhesion and stress fiber formation, thus promoting the rounded shape by increasing the internal contractile force.. Lim et al. now show that ...
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around). It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility. This gene encodes a cytosolic protein tyrosine kinase that is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant sequence similarity to kinases from other subfamilies. It also includes a large FERM domain. 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 ...
Western blot analysis. Whole cell lysate for SDS-PAGE and Western blot analysis for FAK expression was prepared as previously reported ( 24). To prepare lysate from dissected in vivo tumors, samples were snap frozen in liquid nitrogen immediately after sacrificing the animals and stored at −80°C. The lysate was incubated on ice in radioimmunoprecipitation assay buffer for 2 h before being homogenized using a mortar and pestle. The homogenized sample was centrifuged, and the supernatant was collected and stored at −80°C. Protein quantification and Western blot for FAK were done as previously reported ( 24). Equal loading was confirmed with β-actin (0.1 μg/mL, Sigma Chemical). Densitometric analysis was done using the Scion Imaging software (Scion Corporation), using total FAK or actin as a control for each sample.. Cytotoxicity assay. The IC50 was determined as described previously ( 23). Briefly, 2,000 cells per well were seeded onto 96-well plates and allowed to adhere overnight, after ...
Interrupting the interplay between cancer cells and extracellular matrix (ECM) is a strategy to halt tumor progression and stromal invasion. Perlecan/heparan sulfate proteoglycan 2 (HSPG2) is an extracellular proteoglycan that orchestrates tumor angiogenesis, proliferation, differentiation and invasion. Metastatic prostate cancer (PCa) cells degrade perlecan-rich tissue borders to reach bone, including the basement membrane, vasculature, reactive stromal matrix and bone marrow. Domain IV-3, perlecans last 7 immunoglobulin repeats, mimics native proteoglycan by promoting tumoroid formation. This is reversed by matrilysin/matrix metalloproteinase-7 (MMP-7) cleavage to favor cell dispersion and tumoroid dyscohesion. Both perlecan and Domain IV-3 induced a strong focal adhesion kinase (FAK) dephosphorylation/deactivation. MMP-7 cleavage of perlecan reversed this, with FAK in dispersed tumoroids becoming phosphorylated/activated with metastatic phenotype. We demonstrated Domain IV-3 interacts with ...
The metastatic lymph node 64 (MLN64) gene was initially identified as highly expressed in the metastatic lymph node from breast cancer. It is localized in q12-q21 of the human chromosome 17 and is often co-amplified with erbB-2. However, the role played by MLN64 in breast cancer remains unclear. In the present study, the expression of MLN64 was examined in a breast cancer cohort using quantitative real-time PCR and immunohistochemical staining. It demonstrated that MLN64 was highly expressed in breast tumours compared to corresponding background tissues at both transcript level and protein level. The elevated level of MLN64 transcripts was correlated with the poor prognosis and overall survival of the patients. A panel of breast cancer cell sublines was subsequently developed by knockdown of MLN64 expression. Loss of MLN64 expression in MCF-7 cells resulted in a significant reduction of cell growth (absorbance for MCF-7ΔMLN64 being 0.87±0.07, ...
NSCLC remains a significant clinical challenge due to the fact that few medical treatments are effective in this disease. It is well known that NSCLC displays either primary or acquired resistance to chemotherapy and targeted therapy. The limitations of current therapies are evident in mutant KRAS NSCLC. For instance, direct inhibitors of oncogenic KRAS lack the specificity needed for their deployment in vivo (47-49). Furthermore, inhibition of the canonical KRAS signaling pathways MEK1/2, PI3K, and mTORC1/2 have not shown benefits in lung cancer patients that justify their FDA approval for clinical use (4). As a consequence, there has been an intense interest in the identification of novel therapeutic targets for mutant KRAS NSCLC.. The data presented in this article lead to several important conclusions: not only is FAK a targetable vulnerability of mutant KRAS lung cancer, but its inhibition also leads to significant radiosensitizing effects that can be exploited in a combination therapy ...
PF 431396 is a dual focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor (IC50 values are 2 and 11 nM respectively).
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.
The molecular mechanism by which cancer-associated fibroblasts (CAFs) confer chemoresistance in ovarian cancer is poorly understood. The purpose of the present study was to evaluate the roles of CAFs in modulating tumor vasculature, chemoresistance, and disease progression. Here, we found that CAFs upregulated the lipoma-preferred partner (LPP) gene in microvascular endothelial cells (MECs) and that LPP expression levels in intratumoral MECs correlated with survival and chemoresistance in patients with ovarian cancer. Mechanistically, LPP increased focal adhesion and stress fiber formation to promote endothelial cell motility and permeability. siRNA-mediated LPP silencing in ovarian tumor-bearing mice improved paclitaxel delivery to cancer cells by decreasing intratumoral microvessel leakiness. Further studies showed that CAFs regulate endothelial LPP via a calcium-dependent signaling pathway involving microfibrillar-associated protein 5 (MFAP5), focal adhesion kinase (FAK), ERK, and LPP. Thus, ...
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 ...
mRNAs localize to specific regions within neurons, where they can be translated to quickly generate large amounts of a protein in the place where it is needed. Due to the large size of neurons, this is much more efficient than translating all mRNAs in a single place and then shipping out each protein to its site of action. But the movement and translation of these mRNAs must be tightly regulated, potentially by extracellular signals such as growth factors.. Tsai et al. discovered that EGF boosts expression of the κ-opioid receptor (KOR) by stimulating both the nuclear export and translation of KOR mRNA. The key to this dual control was an RNA-binding protein called Grb7. EGF prods a phosphatase called SHP-2 to dephosphorylate Grb7 in the nucleus, prompting it to bind KOR mRNA and recruit a protein complex involved in nuclear export. But EGF also stimulated focal adhesion kinase to rephosphorylate Grb7 in the cytoplasm, causing it to release the mRNA for translation into KOR protein.. Senior ...
Human enhancer of filamentation 1, a novel p130,sup,cas,/sup,-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces ...
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) […]. ...
Z3330795 (talk) 16:14, 11 April 2013 (EST)FAK-Focal Adhesion Kinase Antibody --Z3376548 (talk) 16:15, 11 April 2013 (EST) Catenin beta Antibody (6F9) --Z3374087 (talk) 16:15, 11 April 2013 (EST)alpha-2-catenin --Z3331321 (talk) 16:16, 11 April 2013 (EST) Anti-α-E-Catenin Rabbit ...
Z3330795 (talk) 16:14, 11 April 2013 (EST)FAK-Focal Adhesion Kinase Antibody --Z3376548 (talk) 16:15, 11 April 2013 (EST) Catenin beta Antibody (6F9) --Z3374087 (talk) 16:15, 11 April 2013 (EST)alpha-2-catenin --Z3331321 (talk) 16:16, 11 April 2013 (EST) Anti-α-E-Catenin Rabbit ...
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。
FAK兔多克隆抗体(ab4794)可与人样本反应并经WB实验严格验证,被4篇文献引用。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
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 ...
Lung cancer is the most common cancer and also the leading cause of cancer-related death worldwide among both men and women. Small cell lung cancer (SCLC) accounts for 15% of all cases. It is the most aggressive one in its clinical behavior with a 5-year overall survival as low as 5%. Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase which regulates integrin and growth factor signaling pathways involved in cell proliferation, survival, migration, and invasion. FAK is overexpressed and/or activated in many cancers including SCLC. We hypothesized that FAK may represent a good target for therapeutic interventions in SCLC and tested the changes of cell phenotype induced by a FAK inhibitor (PF-228). ...
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
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 ...
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.. ...
In the present study we first elucidated the NTN‐1-mediated signaling pathway in BBB protection following SAH in rats. Our results showed that endogenous NTN‐1 and DCC receptor were upregulated in the early stage after SAH. Exogenous NTN‐1 treatment reduced brain edema and BBB permeability and thereby alleviated neurological deficits after SAH, which were accompanied by an increase in FAK phosphorylation and a decrease in RhoA activity as well as endothelial junction protein upregulation. In contrast, silencing of endogenous NTN‐1 by special siRNA exacerbated brain edema, BBB disruption, and neurological deficits. Furthermore, knockdown DCC using DCC siRNA or inhibition of FAK by Fib‐14 abolished the neuroprotective effects of exogenous NTN‐1 on BBB integrity and brain edema formation, which were associated with the increased RhoA activity and MMP‐9 and the degraded endothelial junction proteins and basal lamina at 24 hours after SAH. Taken together, these findings support our ...
A recently developed stable isotope dilution liquid chromatography-multiple reaction/mass spectrometry method to quantify focal adhesion kinase (FAK) activation loop phosphorylation was used to study endogenous Src kinase activity. This revealed that bis-phosphorylated pTyr576/Tyr577-FAK was a biomarker of Src activity and inactivation in vitro and in cell culture. Mouse embryonic fibroblasts (MEFs) expressing endogenous Src family kinases contained 65% unmodified Tyr576/Tyr577, 33% mono-phosphorylated-pTyr576-FAK, and 6% bis-phosphorylated-pTyr576/pTyr577-FAK. In contrast, MEFs expressing oncogenic Y529FSrc contained 38% unmodified Tyr576/Tyr577-FAK, 29% mono-phosphorylated-pTyr576-FAK, and 19% bis-phosphorylated-pTyr576/pTyr577-FAK. This new method has made it possible to accurately determine the absolute amounts of FAK phosphorylation that occur after Src inhibition in cell culture and in vitro with increasing concentrations of the Src inhibitor ...
Mitogen-induced changes in the actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several proteins in focal adhesions. In this study, we have investigated the role of RAFTK (also termed Pyk2/CAK-β), a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex. Maximal phosphorylation of the proteins participating in this complex occurred within 2 h of HRG stimulation. Analyses of the members of the HRG-stimulated complex revealed that RAFTK associated with p190 RhoGAP (p190), RasGAP, c-Abl as well as with the focal adhesion molecules p130cas and paxillin. c-Abl was found to be associated with RAFTK through the region of RAFTK containing amino acids 419-1009. Site-directed mutagenesis of Y881 aa within the RAFTK sequence abolished the binding of RAFTK to ...
Stress remains a major cause of death throughout the world, especially for patients younger than 45?years. contributes to overwhelming and long term systemic inflammation. In this specific article, we summarize the original measures of innate immune system response to stress and review the complicated coagulation and go with cascades, aswell as the way they interact with one another. Despite improvement in understanding these cascades, effective restorative targets have however found and further study is necessary both to boost survival rates aswell as decrease associated morbidity. strong class=kwd-title Keywords: Coagulation, complement, DAMPs, PAMPS, trauma Introduction Trauma remains among the leading causes of death throughout the world. 4.9 million deaths in 2016 were caused by injuries, 29% of which were road accidents.1 In the USA alone, unintentional injuries became the third leading cause of death across all ages with an annual death rate of 47.4 per 100,000 US standard population2 ...
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 ...
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 ...
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 ...
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.
Interest in tumor invasion, metabolic switch, and adaptive resistance, with particular focus on the mechanisms and therapeutic interventions of focal adhesion kinase (FAK) and insulin-like growth factor (IGF1R)-triggered cell-cell interactions, mitophagy, and survival.. Cancer parasitizes surrounding tissues. Tumor growth depends on a consistent supply of building materials for cell division and an additional space for new cells to occupy. Current observations indicate that tumor eat neighboring normal cells in vitro. Co-culturing cell models, dynamic tracing, and invasion/metastasis reporter mice are used to test the hypothesis of tumor conquering stromal cells. First of all, cancer cells breakdown the extracellular matrix and membrane of a host cell. FAK is accumulated at the edge of the invading cells, and FAK recruits partners to the attacking point. The signal events that lead to the destruction of the cell barrier are currently under investigation. Second, current observations indicate ...
Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53−/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53−/− cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+
Topographical and mechanical properties of adhesive substrates provide important biological cues that affect cell spreading, migration, growth, and differentiation. The phenomenon has led to the increased use of topographically patterned and flexible substrates in studying cultured cells. However, these studies may be complicated by various limitations. For example, the effects of ligand distribution and porosity are affected by topographical features of 3D biological constructs. Similarly, many studies of mechanical cues are compounded with cellular deformation from external forces, or limited by comparative studies of separate cells on different substrates. Furthermore, understanding cell responses to mechanical input is dependent upon reliable measurements of mechanical properties. This work addresses each of these issues. To determine how substrate topography and focal adhesion kinase (FAK) affect cell shape and movement, I studied FAK-null (FAK -/-) and wild type mouse 3T3
The Peptidyl-tRNA Hydrolase 2 (PTRH2) gene codes for a highly conserved mitochondrial protein. This protein prevents the accumulation of dissociated peptidyl-tRNA, and plays an important role in regulating cell survival and death. It promotes cell survival as part of an integrin-signaling pathway for cells attached to the extracellular matrix (ECM), through interaction with focal adhesion kinase (FAK) and subsequent activation of the PI3K-AKT-NFkB pathway. It also induces Bcl-2 transcription that blocks the intrinsic mitochondrial apoptotic pathway. PTRH2 functions as a phosphoprotein that regulates NFkB and ERK signaling. In cells that have lost their attachment to the ECM through anoikos, PTRH2 promotes apoptosis. Upon loss of integrin-mediated cell attachment to the ECM, PTRH2 protein is phosphorylated, is released from the mitochondria into the cytosol, and promotes apoptosis through interactions with transcriptional regulator amino-terminal enhancer of split (AES). Defects in this protein ...
The product encoded by this gene is preferentially expressed in hematopoietic cells and belongs to the paxillin protein family. Similar to other members of this focal-adhesion-associated adaptor-protein family, it has four leucine-rich LD-motifs in the N-terminus and four LIM domains in the C-terminus. It may function in cell type-specific signaling by associating with PYK2, a member of focal adhesion kinase family. As a substrate for a tyrosine kinase in lymphoid cells, this protein may also function in, and be regulated by, tyrosine kinase activity. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009 ...
Researchers from McGill University have revealed that an enzyme called the focal adhesion kinase (FAK) plays a pivotal role in the onset of breast cancer
Focal adhesion kinase and actin regulatory/binding proteins that modulate F-actin organization at the tissue barrier: Lesson from the testis.by Cheng CY, Lie PP, Wong EW, Mruk DD. MiniManuscript.
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 ...
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 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 ...
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 ...
These reputable organizations may also provide additional information to people who need assistance or referrals.. Spine Arthroplasty Society - The international scientific forum of surgeons focusing on non-fusion technologies. It offers non-fusion technology education on spinal stabilization as a consequence of trauma, deformities, as well as degenerative diseases of the spine ...
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"Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through ... similar to those found in other adhesion-related proteins such as focal adhesion kinase (FAK) and vinculin. The remaining ... Cary LA, Han DC, Polte TR, Hanks SK, Guan JL (1998). "Identification of p130Cas as a mediator of focal adhesion kinase-promoted ... Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S, Freedman AS (1997). "The related adhesion focal tyrosine kinase ...
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... also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion- ... a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase". ... Girault JA, Labesse G, Mornon JP, Callebaut I (December 1998). "Janus kinases and focal adhesion kinases play in the 4.1 band: ... focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase ...
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Liang F, Qi RZ, Chang CF (2001). "Signalling of GPI-anchored CD157 via focal adhesion kinase in MCA102 fibroblasts". FEBS Lett ... CD157 has an important role in controlling the migration of leukocytes, the adhesion of leukocytes to blood vessel walls, and ... 2005). "CD157 is an important mediator of neutrophil adhesion and migration". Blood. 104 (13): 4269-78. doi:10.1182/blood-2004- ... 54 (1): 1-4. doi:10.1016/S0165-2478(96)02633-8. PMID 9030974. Wimazal F, Ghannadan M, Müller MR, et al. (2000). "Expression of ...
"Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase". Nature Cell Biology. 7 (6): ... Dynamic microtubules are also required to trigger focal adhesion disassembly, which is necessary for migration. It has been ... Ren XD, Kiosses WB, Schwartz MA (February 1999). "Regulation of the small GTP-binding protein Rho by cell adhesion and the ... 19 (1): 31-5. doi:10.1016/j.ceb.2006.12.009. PMID 17184986. Jiang S, Narita A, Popp D, Ghoshdastider U, Lee LJ, Srinivasan R, ...
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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 ... kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of receptors for ... Caenorhabditis elegans protein phosphatase ptp-1. Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low ...
Abbi S, Ueda H, Zheng C, Cooper LA, Zhao J, Christopher R, Guan JL (Sep 2002). "Regulation of focal adhesion kinase by a novel ... Ueda H, Abbi S, Zheng C, Guan JL (Apr 2000). "Suppression of Pyk2 kinase and cellular activities by FIP200". The Journal of ... Maucuer A, Camonis JH, Sobel A (Apr 1995). "Stathmin interaction with a putative kinase and coiled-coil-forming protein domains ... "Suppression of Pyk2 kinase and cellular activities by FIP200". The Journal of Cell Biology. 149 (2): 423-30. doi:10.1083/jcb. ...
Goldmann WH (2003). "p56(lck) Controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK))". ... 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". ... lck+Kinase at the US National Library of Medicine Medical Subject Headings (MeSH) Overview of all the structural information ... It is a member of the Src family of tyrosine kinases. Lck is most commonly found in T cells. It associates with the cytoplasmic ...
February 2018). "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase ... ISBN 978-1-934115-46-6. Smith RJ, Shearer AE, Hildebrand MS, Van Camp G (January 2014). "Hereditary Hearing Loss and Deafness ... 401 (1): 143-51. doi:10.1016/j.ydbio.2014.12.023. PMID 25553982. Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale ... 9 (1): 578. Bibcode:2018NatCo...9..578T. doi:10.1038/s41467-018-02938-1. PMC 5805730. PMID 29422613. "Entrez Gene: GJB2 gap ...
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protein tyrosine kinase binding. Cellular component. • cytoplasm. • cell junction. • cytoskeleton. • focal adhesion. • cell ... These include association with FAK and Src family kinases at focal adhesions to transmit integrin-initiated signals to ... "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 ...
"Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling". J. ... focal adhesion. • melanosome. • receptor complex. • cell membrane. • integral component of plasma membrane. • ruffle membrane. ... activation of protein kinase activity. • leukocyte migration. • cell adhesion mediated by integrin. • platelet activation. • ... substrate adhesion-dependent cell spreading. • negative regulation of lipid transport. • cell-matrix adhesion. • GO:0022415 ...
"Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling". J. ... Niu JK, Zhang WJ, Ye LY, Wu LQ, Zhu GJ, Yang ZH, Grau GE, Lou JN (2007). "The role of adhesion molecules, alpha v beta 3, alpha ... Zhou M, Graham R, Russell G, Croucher PI (2001). "MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the ... Liliental J, Chang DD (1998). "Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit". J. Biol ...
Rho GTPase activating protein 26 (ARHGAP26) also known as GTPase Regulator Associated with Focal Adhesion Kinase (GRAF) is a ... Pillay TS, Sasaoka T, Olefsky JM (1995). "Insulin stimulates the tyrosine dephosphorylation of pp125 focal adhesion kinase". J ... "An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Mol. Cell. Biol. ... the GTPase regulator associated with focal adhesion kinase, are mediated by Rho". J. Cell Sci. 112 (2): 231-42. PMID 9858476. ...
Naik MU, Naik UP (2004). "Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet ... 2000). "Adhesion induced expression of the serine/threonine kinase Fnk in human macrophages". Oncogene. 19 (42): 4832-9. doi: ... Ma S, Liu MA, Yuan YL, Erikson RL (2003). "The serum-inducible protein kinase Snk is a G1 phase polo-like kinase that is ... however this protein is known to interact with DNA-dependent protein kinase and may play a role in kinase-phosphatase ...
Hayashi I, Vuori K, Liddington RC (2002). "The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix ... and sufficient for localizing focal adhesion kinase (FAK) to focal adhesions. It forms a four-helix bundle structure and ... Focal adhesion targeting (FAT) domain The FAT-like C-terminal domain is highly conserved in focal adhesion proteins, ... In response to integrin activation, FAK or the related kinase RAFTK recruits NEDD9 into a focal adhesion site, binds it via the ...
Rho family GTPases, integrin linked kinase and focal adhesion kinase (FAK) activate cyclin D gene in response to integrin. ... October 2000). "The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3beta and cAMP- ... The MAP kinase ERK activates the downstream transcription factors Myc, AP-1 and Fos which in turn activate the transcription of ... Cyclin D is regulated by the downstream pathway of mitogen receptors via the Ras/MAP kinase and the β-catenin-Tcf/LEF pathways ...
... promotes motility of cancer cells through activation of focal adhesion kinase (FAK)". Biotechnol. Lett. 28 (24): 2057-63. doi: ... 307 (1): 52-63. doi:10.1016/s0006-291x(03)01121-5. PMID 12849980. Shim H, Lee H, Jeoung D (2006). "Cancer/testis antigen cancer ...
Abdel-Ghany M, Cheng HC, Elble RC, Pauli BU (2002). "Focal adhesion kinase activated by beta(4) integrin ligation to mCLCA1 ... Chloride channel accessory 1 is a protein that in humans is encoded by the CLCA1 gene. This gene encodes a member of the ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Hegab AE, Sakamoto T, Uchida Y, et al. (2004). "CLCA1 gene polymorphisms in ... 2000). "HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation". Proc. Natl ...
... interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... 6 (1): 79-85. doi:10.3758/CABN.6.1.79. PMID 16869232.. *^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). " ...
focal adhesion. • transcription factor complex. • cell-cell adherens junction. • Z disc. • stress fiber. • filamentous actin. ... Vallenius T، Mäkelä TP (2003). "Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein.". J. Cell ... cell-cell adhesion. • positive regulation of nucleic acid-templated transcription. • heart development. • actin cytoskeleton ... cadherin binding involved in cell-cell adhesion. • actin binding. • muscle alpha-actinin binding. ...
... showed the specificity of Rho in the stimulation of focal adhesions and stress fibres formation in fibroblasts in the ... and two kinases of the JNK MAP kinase pathway (MLK2 and MKK7). He then determined that CNK1 acts together with these four ... The inhibition of Rho by C3 transferase ribosylation resulted in an inhibition of focal adhesion and stress fibre assembly, but ... "The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth ...
focal adhesion. • spindle pole centrosome. • intracellular ribonucleoprotein complex. • cariolinfa. • centro organizador dos ... protein kinase inhibitor activity. • histone binding. • Tat protein binding. • NF-kappaB binding. • ligação a proteínas ... protein kinase binding. • core promoter binding. • RNA polymerase II transcription coactivator activity. • transcription factor ... positive regulation of protein kinase activity. • positive regulation of transcription from RNA polymerase II promoter. • ...
Namun beberapa kondisi lain dapat menimbulkan gejala yang sangat serupa dengan TIA, seperti focal seizure activity, migraine ... "Thrombolysis with tissue plasminogen activator alters adhesion molecule expression in the ischemic rat brain". Department of ... Sel TH1 CD4+ dengan sekresi sitokina pro-radang termasuk IL-2, IL-12, IFN-γ dan TNF-α dapat memperburuk efek yang ditimbulkan ... Niken Prathivi (July 1, 2014). "Detecting and dealing with strokes".. *^ Donnan GA, Fisher M, Macleod M, Davis SM (May 2008). " ...
Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM (July 1999). "PTEN interactions with focal adhesion kinase and ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... 6 (1): 79-85. doi:10.3758/CABN.6.1.79. PMID 16869232.. *^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). " ...
... stimulates the focal adhesion kinase (FAK) signaling pathway which leads to prostate cancer cell growth and survival.[65] ... Retrieved 1 July 2014.. *^ a b c d e f g h i j k l m World Cancer Report 2014. World Health Organization. 2014. pp. Chapter ... Retrieved 1 July 2014.. *^ a b c d e f g h i j k "Prostate Cancer Treatment (PDQ) - Patient Version". National Cancer Institute ... 90 (6): 340-1. PMC 1296316 . PMID 9227387.. *^ a b Wei ZF, Xu H, Wang H, Wei W, Cheng W, Zhou WQ, Ge JP, Zhang ZY, Gao JP, Yin ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... They are active or 'ON' when it is bound to GTP and inactive or 'OFF' when bound to GDP.[1] Activation and deactivation of ...
"Involvement of focal adhesion kinase in invasin-mediated uptake". Proc. Natl. Acad. Sci. U.S.A. 95 (23): 13658-63. PMC 24875. ... and the associated accumulation of these proteins in peripheral focal adhesions". EMBO J. 16 (9): 2307-18. PMC 1169832. PMID ... YopH actúa sobre os sitios de adhesión focal ao desfosforilar varios residuos de fosfotirosina na quinase de adhesión focal ( ... Adhesion[editar , editar a fonte]. Y. pseudotuberculosis adhírese fortemente ás células intestinais por medio de proteínas ...
focal adhesion. • mitochondrion. • endoplasmic reticulum. • cell membrane. • extracellular matrix. • collagen-containing ... positive regulation of I-kappaB kinase/NF-kappaB signaling. • positive regulation of cytosolic calcium ion concentration ... positive regulation of cell adhesion. • branching involved in salivary gland morphogenesis. • positive regulation of ... Mishra S, Murphy LJ (June 2004). "Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
RHAMM promotes cancer cell motility through a number of pathways including focal adhesion kinase (FAK), MAP kinase (MAPK), pp60 ... Receptor CD44 participates in cell adhesion interactions required by tumor cells. Although hyaluronan binds to receptor CD44, ... It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated ... c-src), and the downstream targets of Rho kinase (ROK).[22] RHAMM can also cooperate with CD44 to promote angiogenesis toward ...
focal adhesion. • microtubule organizing center. • spindle midzone. • neuron projection. • storage vacuole. • cytoskeleton. • ... mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... epithelial cell-cell adhesion. • sprouting angiogenesis. • nervous system development. • macrophage differentiation. • ...
regulation of cell-cell adhesion. • positive regulation of peptidyl-tyrosine phosphorylation. • regulation of focal adhesion ... activation of transmembrane receptor protein tyrosine kinase activity. • axon guidance. • synaptic membrane adhesion. ... "Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion". Genes ... 1997). "Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor". J. Biol. Chem. 272 ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ... The latter class of complexes is made up of alpha (α), beta (β) and gamma (γ) subunits.[1] In addition, the beta and gamma ... This is accomplished via the Parathyroid hormone 1 receptor (PTH1) in the kidneys and bones, or via the Parathyroid hormone 2 ...
... and focal adhesion kinase from in thrombospondin-treated smooth muscle cells". Journal of Investigative Medicine. 48 (3): 190-7 ... focal adhesion. • plasma membrane. • stress fiber. • uropod. • immunological synapse. • myosin II complex. • extracellular ... it regulates the cellular localization of NM IIA and contributes to the maturation of focal adhesions. Other proteins that are ... but most prominently by Rho-dependent kinase and/or by the calcium-calmodulin-dependent myosin light chain kinase, not only ...
"Differential regulation of Pyk2 and focal adhesion kinase (FAK). The C-terminal domain of FAK confers response to cell adhesion ... Chen HC, Appeddu PA, Parsons JT, Hildebrand JD, Schaller MD, Guan JL (Jul 1995). "Interaction of focal adhesion kinase with ... 1y19: Structural basis for phosphatidylinositol phosphate kinase type I-gamma binding to talin at focal adhesions ... and focal adhesion kinase.[15][16] Talin-1 N-terminal region also binds acidic phospholipids for insertion into lipid bilayers. ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... RETGC-1 has been found to be expressed in higher levels in cones compared to rod cells. Studies have also shown that mutations ... cGMP keeps cGMP-gated channels open, allowing for the entry of calcium into the cell.[1] Like cAMP, cGMP is an important second ... Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ...
... focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase ... 1995). "Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL". J. Biol. Chem. 270 (10): ... "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins". ... "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins". ...
"Specific interactions of neuronal focal adhesion kinase isoforms with Src kinases and amphiphysin". J. Neurochem. (England) 84 ... "Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic ... "Site-specific phosphorylation of platelet focal adhesion kinase by low-density lipoprotein". Biochem. J. (England) 369 (Pt 2): ... "Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte ...
It increases the expression or changes the function of certain adhesion molecules (α4/β7 integrin) in lymphocytes, so they ... Also, it indirectly inhibits several T lymphocyte-specific kinases and phosphatases, hence preventing their transition from G1 ... focal segmental glomerulosclerosis, Crohn's disease, Behcet's Disease, pemphigus, and ulcerative colitis). ... epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators ...
focal adhesion. • transcription regulator complex. • chromatin. • RNA polymerase II transcription regulator complex. ... "Identification of sites on chromosomal protein HMG-I phosphorylated by casein kinase II". FEBS Letters. 257 (1): 101-4. doi ... "Entrez Gene: HMGA1 high mobility group AT-hook 1".. *^ Semple RK (2009). "From bending DNA to diabetes: the curious case of ... 7 (1): 26-43. PMID 15875659.. *. Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z (Feb 2006). "Cellular co- ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase), one of the first few kinases ... an enzyme called protein kinase A (PKA).[12]. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ... Main article: function of cAMP-dependent protein kinase. ... G protein-coupled receptor kinase. *AMP-activated protein ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... Cyclins, when bound with the dependent kinases, such as the p34/cdc2/cdk1 protein, form the maturation-promoting factor. MPFs ... cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Nurse won the 2001 Nobel Prize in Physiology or Medicine for their discovery of cyclin and cyclin-dependent kinase.[17] ...
Cell adhesion[edit]. Many cells bind to components of the extracellular matrix. Cell adhesion can occur in two ways; by focal ... adhesion kinase (FAK), talin, vinculin, paxillin, α-actinin, GTPases etc.) which cause changes in cell shape and actomyosin ... The molecular mechanisms behind durotaxis are thought to exist primarily in the focal adhesion, a large protein complex that ... This cell-to-ECM adhesion is regulated by specific cell-surface cellular adhesion molecules (CAM) known as integrins. Integrins ...
... activated platelets promote the adhesion of cancer cells to activated endothelial cells lining blood vessels using adhesion ... Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical ... have a spindle-shaped morphology and interact with each other only through focal points.[4] Epithelial cells express high ... Following adhesion to the endothelium, the metastatic cancer cell exits the bloodstream at the secondary site to begin ...
Hamel, W; Magnelli, L; Chiarugi, VP; Israel, MA (June 1996). "Herpes simplex virus thymidine kinase/ganciclovir-mediated ... "Developmental exposure to estrogens alters epithelial cell adhesion and gap junction proteins in the adult rat prostate" ... of the herpes simplex virus thymidine kinase/ganciclovir system in vitro". Gene Ther. 3 (1): 85-92. PMID 8929915.. ... 142 (1): 359-69. doi:10.1210/en.142.1.359. PMID 11145599.. *^ Kelley, Robert O.; Vogel, Kathryn G.; Crissman, Harry A.; Lujan, ...
focal adhesion. • melanosome. • ruffle membrane. • trans-Golgi network. • cnewyllyn cell. • cell projection. • extrinsic ... protein kinase binding. • nucleotide binding. • GTP binding. • Rab GTPase binding. • protein serine/threonine kinase activity. ... positive regulation of focal adhesion assembly. • regulation of fibroblast migration. • positive regulation of lamellipodium ... positive regulation of phosphatidylinositol 3-kinase activity. • positive regulation of substrate adhesion-dependent cell ...
... 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.. Ren XR1, Ming GL, Xie Y, Hong Y, Sun DM, Zhao ZQ, Feng Z, Wang Q, Shim S, Chen ZF ... 1. Department of Pathology, University of Alabama, Birmingham, Alabama 35294, USA.. Abstract. Netrins are a family of secreted ... Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth ...
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through ... Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through ... Focal adhesion kinase 1. A, B. 369. Gallus gallus. Mutation(s): 0 Gene Names: FAK1, FAK, PTK2. EC: 2.7.1.112 (PDB Primary Data ... Crystal Structure of the FERM Domain of Focal Adhesion Kinase. Ceccarelli, D.F., Song, H.K., Poy, F., Schaller, M.D., Eck, M.J. ...
... 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. ... Xiu-Rong Ren 1 , Guo-Li Ming, Yi Xie, Yan Hong, Dong-Mei Sun, Zhong-Qiu Zhao, Zhu Feng, Qiang Wang, Sangwoo Shim, Zhou-Feng ... Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth ...
... adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell ... The carboxy-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to ... Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is ... Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. ...
... regulates spermatid adhesion in the testis via dephosphorylation of focal adhesion kinase and the nectin-3 adhesion protein ... focal adhesion kinase (FAK)-Tyr^397 and retention of nectin-3 adhesion protein at the apical ES. To further investigate the ... The expression of sFRP1 is tightly regulated in adult rat testis to control spermatid adhesion and sperm release at spermiation ... implying that sFRP1 might be correlated with elongated spermatid adhesion conferred by the apical ES before spermiation. Indeed ...
Focal Adhesion Protein-Tyrosine Kinases [D08.811.913.696.620.682.725.049]. *Focal Adhesion Kinase 1 [D08.811.913.696.620.682. ... "Focal Adhesion Kinase 1" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins ... This graph shows the total number of publications written about "Focal Adhesion Kinase 1" by people in this website by year, ...
... focal adhesion; FAK, focal adhesion kinase; FRNK, FAK-related non-kinase; GST, glutathione S-transferase; IPTG, isopropyl β-d- ... at focal adhesions. PP1δ also co-immunoprecipitated with the focal adhesion kinase (FAK) and the αv-integrin. In the present ... The association was confirmed by the ability to GST-FAK-related non-kinase (FRNK) to pull-down PP1δ from fibroblasts extract. ... FAK displays consensus sequences for phosphorylation by cell division cycle kinase-2-cyclin B, and might be a PP1 substrate. In ...
Focal Adhesion Kinase, a Downstream Mediator of Raf-1 Signaling, Suppresses Cellular Adhesion, Migration, and Neuroendocrine ... Focal Adhesion Kinase, a Downstream Mediator of Raf-1 Signaling, Suppresses Cellular Adhesion, Migration, and Neuroendocrine ... Focal Adhesion Kinase, a Downstream Mediator of Raf-1 Signaling, Suppresses Cellular Adhesion, Migration, and Neuroendocrine ... Focal Adhesion Kinase, a Downstream Mediator of Raf-1 Signaling, Suppresses Cellular Adhesion, Migration, and Neuroendocrine ...
Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase that localizes to focal adhesions, sites of integrin ... Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 2005;6:56-68. ... Focal adhesion kinase is negatively regulated by phosphorylation at tyrosine 407. J Biol Chem 2007;282:10398-404. ... Expression of focal adhesion kinase in normal and pathologic human prostate tissues. Prostate 2002;53:124-32. ...
... phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion ... phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion ... phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion ... phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion ...
An important tyrosine kinase found in focal adhesions is the focal adhesion kinase (FAK). FAK is a 125 kDa cytoplasmic tyrosine ... "Cloning and characterization of cell adhesion kinase β, a novel protein- tyrosine kinase of the focal adhesion kinase subfamily ... specific focal adhesion kinase targeting and focal adhesion assembly function," Molecular and Cellular Biology, vol. 26, no. 12 ... "Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase," Nature Cell Biology, vol. 7, ...
Focal adhesion kinase (FAK) is important for the metastasis of cancer cells. Results from this study show that osthole can not ... Ding, L.; Sun, X.; You, Y.; Liu, N.; Fu, Z. Expression of focal adhesion kinase and phosphorylated focal adhesion kinase in ... Parsons, J.T.; Martin, K.H.; Slack, J.K.; Taylor, J.M.; Weed, S.A. Focal adhesion kinase: A regulator of focal adhesion ... Focal adhesion kinase (FAK) is important for the metastasis of cancer cells. Results from this study show that osthole can not ...
This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between ... adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell ... Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is ... The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to ...
Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 ... Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes. Circ Res. 2003; ... Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity. Am J Physiol Heart ... Phosphorylation of focal adhesion kinase at tyrosine 861 is crucial for Ras transformation of fibroblasts. J Biol Chem. 2004; ...
PTK2 protein tyrosine kinase 2, isoform CRA_a. Homo sapiens (Human). Loading... ... Proteins matched: Focal_adhesion_target_reg (PD006413) This signature appears in the following proteins: Showing 1 to 20 of 975 ... Protein-tyrosine kinase 2-beta. Rattus norvegicus (Rat). Loading... Q00944 3D Focal adhesion kinase 1. Gallus gallus (Chicken) ... Protein-tyrosine kinase 2-beta. Homo sapiens (Human). Loading... Q91738 Focal adhesion kinase 1. Xenopus laevis (African clawed ...
Actin reorganization and focal adhesion formation induced by Rho-kinase. (A) Actin reorganization caused by Rho-kinase. Actin ... new focal adhesions appeared and increased in number (2). Microinjection of GST-CAT induced focal adhesion formation. ... Thus, Rho-kinase appears to mediate signals from Rho and to induce the formation of stress fibers and focal adhesions. ... Taken together, these findings strongly suggest that Rho-kinase regulates the formation of stress fibers and focal adhesions in ...
As a member of the focal adhesion kinase family, FAK2 has been reported to be mainly localized at the focal adhesions and ... focal adhesion kinase. TKI. tyrosine kinase inhibitors. mTOR. mammalian target of rapamycin.. ... This analysis revealed that several tyrosine kinase-mediated signaling pathways, such as focal adhesion kinase, ERBB, ... 2005) Focal adhesion kinase: in command and control of cell motility. Nat. Rev. Mol. Cell Biol. 6, 56-68. ...
Focal Adhesion Kinase) Mouse anti-Human, Unlabeled, Clone: 150µg; Unlabeled. ... Focal Adhesion Kinase (FAK) is a cytoplasmic tyrosine kinase that colocalizes with integrins in focal adhesions. This cellular ... FAK (pY397) (Focal Adhesion Kinase) Mouse anti-Human, Unlabeled, Clone: 14, BD ... FAK (pY397) (Focal Adhesion Kinase) Mouse anti-Human, Unlabeled, Clone: 14, BD ...
5 Focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase, is involved in the regulation of the vascular ... Inhibition of Focal Adhesion Kinase (FAK) by Fib‐14 reversed the protective effects of exogenous Netrin‐1 (NTN‐1) on blood‐ ... Focal adhesion kinase is required for blood vessel morphogenesis. Circ Res. 2003;92:300-307. ... Focal adhesion kinase inhibitor was administered by intraperitoneal injection at 1 hour prior to SAH. Neurological scores, ...
... focal adhesion kinase (FAK), is thought to contribute to this phenotype. FAK localizes in focal adhesion plaques and has a role ... Frisch SM, Vuori K, Ruoslahti E, Chan-Hui P. Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol ... Qi JH, Claesson-Welsh L. VEGF-induced activation of phosphoinositide 3-kinase is dependent on focal adhesion kinase. Exp Cell ... Src-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling. Mol Cell Biol ...
Attenuation of focal adhesion kinase reduces lipopolysaccharide-induced inflammation injury through inactivation of the Wnt and ... infantile pneumonia lipopolysaccharides focal adhesion kinase Wnt and NF-κB pathways new therapeutic target ... In this study, we preliminarily explored the function and mechanism of focal adhesion kinase (FAK) in regulation of ... Heffler, M., Golubovskaya, V. M., Dunn, K. M. B., and Cance, W. (2013) Focal adhesion kinase autophosphorylation inhibition ...
Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Proc Natl Acad Sci U S A 1995; ... Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a major role in mediating signal transduction by ... Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol 1996; 134: 793-9. ... Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 2005; 6: 56-68. ...
Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a ... in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and ... Focal adhesion kinase: in command and control of cell motility Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68. doi: 10.1038/nrm1549 ... Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a ...
... cell apoptosis via focal adhesion kinase dephosphorylation and focal adhesion disassembly independent of focal adhesion kinase ... cell apoptosis via focal adhesion kinase dephosphorylation and focal adhesion disassembly independent of focal adhesion kinase ... Focal adhesion kinase (FAK) is thought to play a key role in maintaining focal adhesion function and cell survival, whereas ... but did not induce FAK dephosphorylation or rapid focal adhesion disruption, and instead caused a slower loss of focal ...
Crystal Structure Analysis of Focal Adhesion Kinase with a Methanesulfonamide Diaminopyrimidine Inhibitor ... Roberts, W.G. et al., Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer ... Crystal Structure Analysis of Focal Adhesion Kinase with a Methanesulfonamide Diaminopyrimidine Inhibitor. Coordinates. PDB ... YAM.1: 20 residues within 4Å:*. Chain A: R.13, I.15, G.16, E.17, V.23, Q.25, A.39, V.71, M.86, E.87, L.88, C.89, G.92, R.137, N ...
Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. Journal of ... Requirement of phosphatidylinositol 3-kinase in focal adhesion kinase-promoted cell migration. Journal of Biological Chemistry ... Focal Adhesion Kinase (FAK) transmits the signal, produced as a result of Integrin-ECM binding, to cell-interior. FAK is a non- ... Focal Adhesion Kinase Small Interfering RNA (SiRNA) Treatment. Human breast cancer cell line MDA-MB-231 were seeded in 35 mm ...
SRC-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling. Mol Cell Biol ... Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase. Carcinogenesis ... The Chemopreventive Bioflavonoid Apigenin Inhibits Prostate Cancer Cell Motility through the Focal Adhesion Kinase/Src ... The Chemopreventive Bioflavonoid Apigenin Inhibits Prostate Cancer Cell Motility through the Focal Adhesion Kinase/Src ...
Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005;6(1):56-68. doi: 10.1038/nrm1549. ... Insulin stimulates the tyrosine dephosphorylation of pp125 focal adhesion kinase. J Biol Chem. 1995;270(3):991-4. doi: 10.1074/ ... Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. ... Look at a tyrosine kinase. Nature. 1994;372(6508):726-7. doi: 10.1038/372726a0.PubMedGoogle Scholar ...
Focal Adhesion Kinase 1. Introduction 2. Biological and Physiological Significance of FAK ...
Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Proc. Natl. Acad. Sci. USA. 92: ... Protein kinase C αvβ5-dependent cytoskeletal associations and focal adhesion kinase phosphorylation. J. Cell Biol. 134:1323- ... Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. USA. 91 ... endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase ...
  • Netrin-1 induced FAK and DCC tyrosine phosphorylation. (nih.gov)
  • Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2 /FAK1 phosphorylation and signaling. (rcsb.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)
  • Syndecan-4 modulates focal adhesion kinase phosphorylation. (umassmed.edu)
  • FAK displays consensus sequences for phosphorylation by cell division cycle kinase-2-cyclin B, and might be a PP1 substrate. (biochemj.org)
  • We previously reported that Abi-1 (Abl interactor 1) promotes phosphorylation of Mena and BCAP (B-cell adaptor for phosphoinositide 3-kinase) by bridging the interaction between c-Abl and the substrate. (biochemj.org)
  • These results suggest that the phosphorylation and dephosphorylation cycle of VASP by the Abi-1-bridged mechanism regulates association of VASP with focal adhesions, which may regulate adhesion of Bcr-Abl-transformed leukaemic cells. (biochemj.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)
  • Western blot analysis was used to assess the phosphorylation of MAP kinases. (pubmedcentralcanada.ca)
  • Examination of FAK activation revealed that β 1 integrin was required for stretch-induced phosphorylation of FAK at Y 397 and Y 925 , but not Y 861 . (pubmedcentralcanada.ca)
  • The binding of extracellular matrix ligands to integrins triggers autophosphorylation at Tyr-397, and activation of FAK through phosphorylation of Tyr residues (Tyr-576 and Tyr577) in the kinase domain activation loop. (fishersci.com)
  • For example, cell adhesion to a fibronectin substratum involves concurrent activation of Src and phosphorylation of the FAK activation loop. (fishersci.com)
  • In addition, phosphorylation of other Tyr residues (Tyr-925, and Tyr-861) creates binding sites for SH2 domains of intracellular signaling molecules such as Src, PI3 kinase, and Grb2. (fishersci.com)
  • Thus, FAK activity is regulated by a complex set of phosphorylation sites, and thisphospho-regulation could be important for cell motility, cell growth, cytoskeletal organization, and adhesion-dependent cell survival. (fishersci.com)
  • The effect of staurosporine was very potent with striking inhibition of Tyr 861 and Tyr 397 phosphorylation and focal adhesion disruption occurring in the range 10-100nM. (portlandpress.com)
  • Selective inhibition of a known target of staurosporine, protein kinase C, using GF109203X, and of phosphoinositide 3′-kinase using wortmannin, did not reduce FAK tyrosine phosphorylation at Tyr 861 and Tyr 397 , or cause disruption of focal adhesions. (portlandpress.com)
  • 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)
  • 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)
  • 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)
  • 1992 ). Tyrosine phosphorylation of paxillin and pp125FAKaccompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. (biologists.org)
  • FAK is activated by phosphorylation at tyrosine 397 in response to integrin clustering which can be induced by cell adhesion or antibody cross-linking or via G-protein-coupled receptor (GPCR) occupancy by ligands such as bombesin or lysophosphatidic acid (2-3). (novusbio.com)
  • Phosphorylation of FAK Tyr-397 creates a binding site for Src-family kinases, and phosphorylation of FAK Tyr-576/Tyr-577 in the kinase domain activation loop enhances catalytic activity (4). (novusbio.com)
  • Meanwhile, we present evidence that GPR56 inhibits fibronectin deposition and its downstream signaling, such as phosphorylation of focal adhesion kinase (FAK), during this process. (frontiersin.org)
  • 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)
  • Pro- and anti-migratory effects of CD9 have been linked to adhesion-dependent signalling pathways, including phosphorylation of FAK (focal adhesion kinase) and activation of phosphoinositide 3-kinase, p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). (biochemsoctrans.org)
  • DCC and neogenin, two of the netrin-1 receptors, have recently been shown to have sites for tyrosine phosphorylation (at Y1420 on DCC) and are likely interacting with Src family kinases in regulating responses to netrin-1. (wikipedia.org)
  • Akt directly regulates focal adhesion kinase through association and serine phosphorylation: implication for pressure-induced colon cancer metastasis. (semanticscholar.org)
  • The IGF-1 induced the activation of canonical signaling pathways through the IGF-1R phosphorylation. (arvojournals.org)
  • 2 Upon IGF-1 binding, the activated IGF-1R promotes phosphorylation of specific cytosolic substrates, then the IGF-1 signal is transmitted to two downstream pathways: extracellular signal-regulated kinases 1 and 2 (ERK 1/2) and phosphatidylinositol 3-kinase (PI3K/AKT). (arvojournals.org)
  • We investigated whether signaling events mediated by the RhoA/Rho-associated coiled coil-containing kinase (ROCK) pathway are involved in regulation of stretch-induced FAK phosphorylation at Tyr 397 in neonatal rat ventricular myocytes (NRVMs). (physiology.org)
  • Blockade of RhoA/ROCK signaling by pharmacological inhibitors of RhoA ( Clostridium botulinum C3 exoenzyme) or ROCK (Y-27632, 10 μmol/l, 1 h) markedly attenuated stretch-induced FAK and ERK1/2 phosphorylation. (physiology.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)
  • 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)
  • 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)
  • 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)
  • MEK kinase I (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase involved in Bcr-Abl signal transduction. (nii.ac.jp)
  • METHODS: We studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect cell proliferation, mitogen-activated protein kinase (MAPK) activation, and expression of G1-phase regulatory proteins in cultured rat mesangial cells (MCs). (biomedsearch.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)
  • The protective effects of NTN ‐1 at 24 hours after SAH were also abolished by pretreatment with Deleted in Colorectal Cancer small interfering RNA and focal adhesion kinase inhibitor. (ahajournals.org)
  • Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. (expasy.org)
  • Taken together, these data show that kinase inhibition with an ATP-competitive small molecule inhibitor of FAK decreases the phospho-status in vivo , resulting in robust antitumor activity. (aacrjournals.org)
  • Cycloheximide, the protein synthesis inhibitor, induced PAEC apoptosis more slowly than staurosporine, but did not induce FAK dephosphorylation or rapid focal adhesion disruption, and instead caused a slower loss of focal adhesions and a marked increase in FAK proteolysis. (portlandpress.com)
  • By binding with scavenger receptor class B type 1 (SCARB1), reconstituted high-density lipoprotein-nanoparticles (rHDL-NPs) were effective in delivering miR-204-5p inhibitor (miR-204-5p-inh) to tumor sites to suppress tumor growth. (nature.com)
  • Administration of the FAK inhibitor Y15 perturbed the proliferation of melanoma metastases, supporting a causative link between the cell adhesion defect induced by GPR56 and its inhibition of metastatic growth. (frontiersin.org)
  • Abstract Background GSK2256098 is a novel oral focal adhesion kinase inhibitor. (deepdyve.com)
  • In addition to being a potent FAK inhibitor, study findings have demonstrated that VS-6063 also inhibits the activity of PYK2, a closely related protein kinase and only other member of the FAK family. (corporate-ir.net)
  • The IGF-1 effect on MMP-2 was abolished by an IGF-1R blocking antibody, αIR3, as well as by the PI3-kinase inhibitor, LY294002. (arvojournals.org)
  • The IGF-1 increased the migratory capacity of MGCs, which was blocked by the GM6001 MMP inhibitor, LY294002 and αIR3. (arvojournals.org)
  • CureFAKtor Pharmaceuticals Demonstrates Novel Focal Adhesion Kinase (FAK) Inhibitor C4 Analogs Inhibited Pancreatic Cancer Tumor Growth as Sin. (bio-medicine.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)
  • also known as PTK2 protein tyrosine kinase 2) is important in cell migration, as its signaling pathways are key to the formation of focal adhesions that aid in the adhering of cells to the extracellular matrix. (biolegend.com)
  • Huh7 cells were stained with anti-PTK2 rabbit purified polyclonal antibody 1:1200 and anti-FLT1 mouse monoclonal antibody 1:50. (abnova.com)
  • 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)
  • Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. (hindawi.com)
  • We also will highlight several important tyrosine kinases and other signaling proteins that are known to control the formation and function of these adhesion structures, and we will discuss their role in pathophysiology. (hindawi.com)
  • Although focal adhesions, podosomes, and invadopodia share common signaling proteins, they are distinct in cellular architecture and function (summarized in Table 1 ). (hindawi.com)
  • Target proteins, the functions of which are modulated by Rho, include protein kinase N (PKN) ( 9 ), Rho-kinase ( 10 ) [also called Rho-binding kinase ( 11 )], and the myosin-binding subunit (MBS) of myosin phosphatase ( 12 ). (sciencemag.org)
  • FAK's ability to bind numerous structural and signaling proteins via a variety of interactions is important for FAK activation level, and for FAK interaction with a variety of substrates localized to sites of cell adhesion. (fishersci.com)
  • Thirteen proteins were found to be affected by mechanical stimulation including Galectin-1, Annexin III, and RhoGDI. (ku.dk)
  • The deduced aa sequence of FAK p125 has shown it to be a cytoplasmic protein tyrosine kinase whose sequence and structural organization are unique as compared to other proteins described to date. (biosave.com)
  • Apigenin treatment leads to formation of "exaggerated filopodia," which show accumulation of focal adhesion proteins at their tips. (aacrjournals.org)
  • Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. (mdpi.com)
  • Recently, studies on Etk/BMX, a member of the Btk family of tyrosine kinases, have shown that the activation of Etk by extracellular matrix proteins is regulated by FAK and requires an interaction between the PH domain of Etk and the FERM domain of FAK (Chen, 1994). (biologists.org)
  • The observed increase in phosphotyrosine content of focal adhesion-associated proteins, in response to integrin engagement, indicates a role for integrin-regulatable tyrosine kinase(s) in cytoskeletal re-organisation. (biologists.org)
  • We have shown that vinculin, pp125FAK and tyrosine-phosphorylated proteins are localised in focal adhesions during this time period. (biologists.org)
  • Cell lysates from Huh7.5.1 cells were incubated with purified GST-claudin-1 tail or GST, and proteins were pulled down with glutathione-Sepharose beads. (asm.org)
  • Candidate claudin-1 tail-interacting proteins were the GST-claudin-1-tail interactome. (asm.org)
  • The direct interaction of DEP-1 with VE-cadherin is likely to be of physiological relevance since both proteins are expressed in endothelial cells. (bireme.br)
  • Here, we report that fibrillar Aβ-induced neuronal dystrophy is mediated by the activation of focal adhesion (FA) proteins and the formation of aberrant FA structures adjacent to Aβ deposits. (jneurosci.org)
  • Vasoactive effects of soluble matrix proteins and integrin-binding peptides on arterioles are mediated by α v β 3 and α 5 β 1 integrins. (rupress.org)
  • A widely studied recognition site on ECM proteins, including vitronectin (VN) and fibronectin (FN) ( Schwarzbauer, 1991 ), is the tripeptide Arg-Gly-Asp (RGD), which is recognized by a common subset of integrins, including α v β 3 , α 5 β 1 , α v β 5 , and α IIb β 3 . (rupress.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)
  • YopH tyrosine dephosphorylates host cell proteins, such as p130Cas and focal adhesion kinase FAK ( 2 ). (jimmunol.org)
  • The products of lysosomal degradation can then be used for the biosynthesis of new proteins and organelles and as an energy source [ 1 ]. (hindawi.com)
  • Moreover, inhibition of FAK gene expression by a phosphorothioated antisense oligodeoxynucleotide targeting the portion of the gene encoding amino acids 262-268, increased the sensitivity of ZR-75-1, MDA-MB-231 and MCF7 breast cancer cells to treatment with TPT or CPT-11. (bvsalud.org)
  • VS-6063 targets cancer stem cells through potent inhibition of focal adhesion kinase (FAK). (aol.com)
  • Inhibition of FAK and IGF-1R function by knock down of genes and kinase inhibitors have shown to significantly decrease cancer cell proliferation and decrease resistance to chemotherapy and radiation treatment. (ufl.edu)
  • Of significant interest to us is that VS-6063 inhibits the focal adhesion kinase family members FAK and PYK2 which leads to the preferential targeting of cancer stem cells both directly and through inhibition of tumor-associated macrophages in the tumor microenvironment. (corporate-ir.net)
  • 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)
  • 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)
  • 10 ) revealed that YopP/YopJ binds and inactivates members of the MAPK kinase superfamily, which function as upstream MAPK activators. (jimmunol.org)
  • 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)
  • focal adhesions) and serves to transduce signals from integrin receptors and enhance signaling by growth factor receptors ( 8 , 9 ). (aacrjournals.org)
  • FAK activity enhances signaling of many receptor tyrosine kinases that are themselves viable anticancer targets, such as insulin-like growth factor receptor (IGF-IR) ( 11 ), the erbB family ( 12 ), and angiogenesis receptors ( 13 ). (aacrjournals.org)
  • Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a major role in mediating signal transduction by integrins, as well as growth factor receptors, in the regulation of cell adhesion, migration, survival, proliferation, and differentiation in a variety of cells ( 11 , 12 ). (aacrjournals.org)
  • A central question in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and motility. (nih.gov)
  • FAK protein tyrosine kinase activity has also been shown to increase in cells stimulated to grow by use of mitogenic neuropeptides or neurotransmitters acting through G protein coupled receptors. (biosave.com)
  • Clustered integrin receptors and activated paxillin (phosphorylated at Tyr-31) and focal adhesion kinase (phosphorylated at Tyr-297) are mainly detected in dystrophic neurites surrounding Aβ plaque cores, where they colocalize with hyperphosphorylated tau. (jneurosci.org)
  • I ntegrins are heterodimeric receptors (α, β) that mediate cell-extracellular matrix (ECM) 1 and cell-cell adhesion events. (rupress.org)
  • Tetraspanin CD9 is associated with integrin adhesion receptors and it was reported that CD9 regulates integrin-dependent cell migration and invasion. (biochemsoctrans.org)
  • 1 These biological actions are mediated by the IGF-1 receptor (IGF-1R), a member of the tyrosine kinase gene family of growth factor receptors. (arvojournals.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)
  • This cellular localization is directed by a 125 amino acid sequence at the C-terminus called the "Focal Adhesion Targeting" sequence (FAT). (fishersci.com)
  • We determined an increase in expression and changes in cellular localization of Galectin-1, in mechanically stimulated myoblasts. (ku.dk)
  • Localization of p125 by immunofluorescence suggests that it is primarily found in cellular focal adhesions leading to its designation as focal adhesion kinase (FAK). (biosave.com)
  • Staurosporine-induced PAEC apoptosis was detected after 1h and was preceded by disruption and loss of FAK localization to focal adhesions within a few minutes, whereas staurosporine-induced cleavage of FAK occurred only after 8-24h. (portlandpress.com)
  • Fibronectin increases association of FAK with integrin α5β1, Paxillin, Actin, ERK, PI3K and localization at Focal Adhesion sites. (scirp.org)
  • In the present paper, we describe a novel mechanism whereby CD9 specifically controls localization of talin1, one of the critical regulators of integrin activation, to focal adhesions: CD9-deficiency leads to impaired localization of talin1 to focal adhesions and correlates with increased motility of breast cancer cells. (biochemsoctrans.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)
  • The association was confirmed by the ability to GST-FAK-related non-kinase (FRNK) to pull-down PP1δ from fibroblasts extract. (biochemj.org)
  • The small guanosine triphosphatase (GTPase) Rho is implicated in the formation of stress fibers and focal adhesions in fibroblasts stimulated by extracellular signals such as lysophosphatidic acid (LPA). (sciencemag.org)
  • 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)
  • 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)
  • 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)
  • Rho participates in signaling pathways that lead to the formation of actin stress fibers and focal adhesions ( 2 ). (sciencemag.org)
  • Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. (mcponline.org)
  • Integrins regulate cellular behaviors through signaling pathways, including Rho GTPases and kinases. (pnas.org)
  • The β1 integrins regulate numerous cellular functions by signaling through a variety of biochemical pathways ( 1 , 2 ). (pnas.org)
  • FAK is a nonreceptor tyrosine kinase that transduces signaling from a diverse group of stimuli (e.g., integrins, cytokines, chemokines, and growth factors) to control a variety of cellular pathways and processes, including cell proliferation, migration, morphology, and cell survival ( 3 , 4 ). (aacrjournals.org)
  • 21-24 The importance of Fak to the regulation of early gene transcription in response to stretch was demonstrated in neonatal rat cardiac myocytes, 20 indicating that this kinase may coordinate signaling pathways involved in the hypertrophic growth induced by mechanical stress. (ahajournals.org)
  • Netrin-1-dependent regulation of exocytotic events requires the activation of the Erk1/2 and SFK pathways. (jneurosci.org)
  • Focal adhesion kinase (FAK) is a non-receptor protein-tyrosine kinase implicated in signaling pathways involved in cell motility, proliferation and apoptosis (1). (novusbio.com)
  • Among its related pathways are Signaling events mediated by focal adhesion kinase . (genecards.org)
  • The data suggest that α v β 3 and α 5 β 1 integrins are differentially linked through intracellular signaling pathways to the L-type Ca 2+ channel and thereby alter control of Ca 2+ influx in vascular smooth muscle. (rupress.org)
  • Previously, we have shown that FAK (focal adhesion kinase) and IGF-1R (insulin-like growth factor receptor-1) directly interact with each other and this interaction provides activation of crucial signaling pathways that benefit cancer cells. (ufl.edu)
  • In addition, we also show that integrin-induced signalling pathways are necessary for EGF-dependent transcriptional response, demonstrating the requirement of the co-operation between cell-matrix adhesion and EGFR to achieve full biological responses. (biochemsoctrans.org)
  • Several lines of evidence support a role for FAK in the regulation of early gene transcription in response to hypertrophic agonists and mechanical stress ( 10 , 22 , 28 , 38 , 39 ), indicating that this kinase may coordinate the convergence of multiple signaling pathways involved in the hypertrophic growth of cardiac myocytes. (physiology.org)
  • Recently, we have shown that activation of the Raf-1 pathway regulates cell-cell contact in medullary thyroid cancer cells ( 13 ). (aacrjournals.org)
  • Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism" Cancer Res. (freepatentsonline.com)
  • Taken together, these data indicate that IGF-1, through its receptor activation, regulates MGCs' motility by a mechanism that involves the MMP-2 and PI3K signaling pathway. (arvojournals.org)
  • Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. (rcsb.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)
  • Requirement of Ca2+ influx- and phosphatidylinositol 3-kinase-mediated m-calpain activity for shear stress-induced endothelial cell polarity. (semanticscholar.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)
  • FAK is a non-receptor protein tyrosine kinase of 125 kD which directly interacts with β-subunit of integrin molecule, resides within the Focal Adhesion complex and initiates Integrin mediated signaling. (scirp.org)
  • 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)
  • Actin stress fibers are linked to integrins at the inner surface of the plasma membrane through focal adhesions ( 1 , 2 ). (sciencemag.org)
  • Focal Adhesion Kinase (FAK) is a cytoplasmic tyrosine kinase that colocalizes with integrins in focal adhesions. (fishersci.com)
  • The survival of endothelial cells is dependent on interactions between the matrix and integrins mediated through focal adhesions. (portlandpress.com)
  • Integrins are known to participate in cell adhesion as well as cell-surface-mediated signaling. (wikipedia.org)
  • It is probable that at these sites integrins regulate adhesion and at the same time physically constrain and direct the response to soluble growth factors towards proliferation or survival stimuli. (biochemsoctrans.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 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)
  • 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)
  • 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)
  • Our results indicate that MASMC-elaborated ECM, but not their conditioned medium, supported pp125FAK tyrosine kinase activation. (biologists.org)
  • 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)
  • 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)
  • Down-regulation of sFRP1 during testicular development was found to coincide with the onset of the first wave of spermiation at approximately age 45 d postpartum, implying that sFRP1 might be correlated with elongated spermatid adhesion conferred by the apical ES before spermiation. (popcouncil.org)
  • Indeed, administration of sFRP1 recombinant protein to the testis in vivo delayed spermiation, which was accompanied by down-regulation of phosphorylated (p)-focal adhesion kinase (FAK)-Tyr^397 and retention of nectin-3 adhesion protein at the apical ES. (popcouncil.org)
  • In this study, we preliminarily explored the function and mechanism of focal adhesion kinase (FAK) in regulation of inflammatory response induced by lipopolysaccharides in A549 cells. (springer.com)
  • Here I seek to summarize the current state of knowledge about FAK and integrate relevant observations into known processes of cell adhesion, migration and growth regulation. (biologists.org)
  • 1992 ). Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. (biologists.org)
  • PTP-PEST plays a key role in the dynamic regulation of focal adhesion contacts in response to extracellular cues. (jneurosci.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)
  • 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)
  • Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. (hindawi.com)
  • Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. (mdpi.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)
  • When DCC is present on the membrane and bound to netrin-1, signals are conveyed that can lead to proliferation and cell migration. (wikipedia.org)
  • Focal adhesions, also known as "focal contacts," were identified over 30 years ago by electron microscopy and described as electron-dense plaques associated with actin filament bundles [ 10 ]. (hindawi.com)
  • This step involves remodeling of the extracellular matrix and of cell-matrix interactions, cell movement mediated by the actin cytoskeleton, and activation of focal adhesion kinase (FAK)/Src signaling. (aacrjournals.org)
  • This highly dynamic and plastic nature of cell-cell adhesions is mediated through the junctional properties of the cells, primarily comprised of vascular endothelial cadherin (VE-cadherin)-based adherens junctions, and tight junctions primarily comprised of claudins, occludins, junctional adhesion molecules (JAMs), cingulin and nectins, many of which form homophilic complexes between endothelial cells and which connect junctions with the actin cytoskeleton [ 2 - 4 ]. (portlandpress.com)
  • The composition and localisation of adhesion molecules combined with the state of junctional tension transmitted to the actin cytoskeleton are central to cell-cell adhesion. (portlandpress.com)
  • MASMC cultured for 16 hours exhibit F-actin stress fibres and focal adhesions. (biologists.org)
  • Furthermore, MASMC exposed to MASMC-ECM displayed a poorly defined F-actin stress fibre network and rudimentary focal adhesions. (biologists.org)
  • On the other hand, FAK activation in neonatal rat ventricular myocytes (NRVMs) by agonists such as endothelin has been demonstrated ( 16 ) to be dependent on activation of the RhoA/Rho-associated coiled coil-containing protein kinase (ROCK) signaling pathway, which drives the assembly and rearrangement of actin filaments. (physiology.org)
  • Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. (rcsb.org)
  • Accordingly, inflammasome activation in response to L. amazonensis is impaired by inhibitors of NADPH oxidase, Syk, focal adhesion kinase, and proline-rich tyrosine kinase 2, and in the absence of Dectin-1. (jimmunol.org)
  • Serine-threonine kinases such as protein kinase C (PKC) and Raf are usually composed of regulatory and catalytic domains ( 16 ). (sciencemag.org)
  • Promotes activation of MAPK1 /ERK2, MAPK3 /ERK1 and the MAP kinase signaling cascade. (rcsb.org)
  • In the present study, we show that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade in BON cells. (aacrjournals.org)
  • The cytoplasmic domain is critical for that activation and involves focal adhesion kinase (FAK), extracellular regulated kinase (ERK1/2), and protein kinase B (AKT/PKB) signaling, further contributing to cancer progression and mediating chemoresistance against first-line therapies. (clinsci.org)
  • However, the downstream mediators of the Raf-1/MEK1/2/ERK/1/2 signaling cascade are unknown. (aacrjournals.org)
  • In vertebrates, Src and the closely related Fyn kinases phosphorylate DCC and form a receptor-bound signaling complex leading to activation of downstream effectors. (semanticscholar.org)
  • Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G(1) phase as a downstream target of focal adhesion kinase (FAK). (genecards.org)
  • In the present paper, we summarize our recent study showing that integrin-dependent adhesion triggers ligand-independent EGFR (epidermal growth factor receptor) activation to transduce downstream signalling. (biochemsoctrans.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)
  • NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. (reactome.org)
  • FAK signaling was disrupted by infecting NRVM with adenovirus expressing FAK-related non-kinase (FRNK). (pubmedcentralcanada.ca)
  • In Drosophila , Ena is a substrate of the tyrosine kinase DAbl ( Drosophila Abl). (biochemj.org)
  • In the present study we have identified VASP, another member of the Mena/VASP family, as an Abi-1-bridged substrate of Abl. (biochemj.org)
  • A hallmark of cancer is the ability for cells to proliferate regardless of adhesion to a substrate ( 1 ). (aacrjournals.org)
  • Focal adhesion kinase was identified as a 125kD substrate for the intrinsic protein tyrosine kinase activity of Src encoded pp60. (biosave.com)
  • Apigenin inhibits the activation of the phosphoinositide 3-kinase/Akt pathway in numerous cell types including prostate cancer cell lines ( 12 , 19 ), potentially by blocking the ATP binding site of phosphoinositide 3-kinase ( 26 ). (aacrjournals.org)
  • Through multifaceted and diverse molecular connections, FAK can influence the cytoskeleton, structures of cell adhesion sites and membrane protrusions to regulate cell movement. (nih.gov)
  • 1988 ). Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. (biologists.org)
  • Here, we show that secreted Frizzled-related protein 1 (sFRP1), a putative tumor suppressor gene that is frequently down-regulated in multiple carcinomas, is a crucial regulatory protein for spermiation. (popcouncil.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. (nih.gov)
  • DCC held a controversial place as a tumour suppressor gene for many years, and is well known as an axon guidance receptor that responds to netrin-1. (wikipedia.org)
  • The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and TrkC . (wikipedia.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)
  • Interacts with EPHA1 (kinase activity-dependent). (rcsb.org)
  • VASP was tyrosine-phosphorylated in Bcr-Abl-positive leukaemic cells in an Abi-1-dependent manner. (biochemj.org)
  • Interestingly, overexpression of both phosphomimetic and unphosphorylated forms of VASP, but not wild-type VASP, impaired adhesion of K562 cells to fibronectin. (biochemj.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)
  • Focal adhesion kinase (FAK) is important for the metastasis of cancer cells. (mdpi.com)
  • Microinjection of the catalytic domain of Rho-kinase into serum-starved Swiss 3T3 cells induced the formation of stress fibers and focal adhesions, whereas microinjection of the inactive catalytic domain, the Rho-binding domain, or the pleckstrin-homology domain inhibited the LPA-induced formation of stress fibers and focal adhesions. (sciencemag.org)
  • Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. (mcponline.org)
  • Mounting evidence suggests that focal adhesion kinase (FAK) plays an essential role in the ability of cells to grow in an adhesion-independent manner ( 2 ). (aacrjournals.org)
  • Numerous studies have provided strong evidence for the existence of mammary stem cells (MaSC) capable of self-renewal and differentiation into the basal and luminal lineages comprising the functional mammary epithelium ( 1 , 2 ). (aacrjournals.org)
  • This study shows a strong association between cell attachment to substratum and activation of beta 1-integrin-signaling with resistance to the camptothecin derivative topotecan (TPT) in breast cancer cells. (bvsalud.org)
  • ZR-75-1 anchorage-dependent breast cancer cell line, its derivative 9D3S suspension cells (9D3S-S), and 9D3S cells attached to fibronectin-coated plates (9D3S-A) were treated with TPT (1 microM) or CPT-11 (40 microM) for 48 h. (bvsalud.org)
  • Programmed cell death (PCD), as shown by poly(ADP-ribose) polymerase (PARP), pro-caspase-3 and pro-caspase-9 cleavage, was observed in 9D3S-S cells but not in ZR-75-1 or 9D3S-A cells. (bvsalud.org)
  • Because p125 focal adhesion kinase (FAK) is a transducer in the beta 1-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. (bvsalud.org)
  • The adhesive properties of endothelial cells are tightly controlled by a complex cascade of signals transmitted from the surrounding environment or from within the cells themselves, with the dynamic nature of cellular adhesion and the regulating signalling networks now beginning to be appreciated. (portlandpress.com)
  • Vasculogenesis, angiogenesis and vascular remodelling are all highly dynamic processes, in which the adhesion of endothelial cells within the vessel wall is tightly controlled. (portlandpress.com)
  • Among up-regulated genes in HCT p53 +/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. (mdpi.com)
  • In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53 +/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. (mdpi.com)
  • Cell lysates from Huh7.5.1 cells were pulled down by GST-claudin-1 tail or GST followed by Western blotting. (asm.org)
  • C) Cell lysates from Huh7.5.1 cells were pulled down by GST-CD81-N-tail, GST-CD81-C-tail, GST-occludin-tail, GST-SRB1-tail, GST-claudin-1 tail or GST with two extra washes. (asm.org)
  • D and E) Immunoblots showing the association of Sec24C with claudin-1 in transfected HEK293T cells by a coimmunoprecipitation assay. (asm.org)
  • HEK293T cells were transfected with Flag-claudin-1, Flag-SRB1, or PCMV-Tag2 empty vector for 48 h. (asm.org)
  • F) Coimmunoprecipitation of endogenous claudin-1 with Sec24C in Huh7.5.1 cells. (asm.org)
  • G) Colocalization of claudin-1 with Sec24C in Huh7.5.1 cells. (asm.org)
  • Huh7.5.1 cells were fixed by PFA and immunofluorescently labeled for claudin-1 (green) and Sec24C (red). (asm.org)
  • B) Huh7.5 cells treated with Sec24C siRNA or a control siRNA for 72 h were stained with antibodies against claudin-1 (green) and the tight junction marker ZO-1 (red). (asm.org)
  • C) Cell surface claudin-1 was quantified by FACS assay in nonpermeabilized cells. (asm.org)
  • D) Intercellular claudin-1 was quantified by FACS assay in permeabilized cells. (asm.org)
  • A) Huh7.5 cells treated with different concentrations of XN for 12 h were fixed with methanol and stained with antibodies against claudin-1 (red) and the tight junction marker ZO-1 (green). (asm.org)
  • Tie2 is a tyrosine kinase receptor located predominantly on vascular endothelial cells that plays a central role in vascular stability. (bireme.br)
  • VSTM ) focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, announced the completion of the dose escalation stage of VS-6063 and paclitaxel in a Phase 1/1b trial in patients with ovarian cancer. (aol.com)
  • 1 King's College London Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, Great Maze Pond, London, United Kingdom. (jci.org)
  • Cancer cells must complete five steps to metastasize to a secondary site: (1) detachment from the primary tumor, (2) intravasation into the circulation, (3) survival in the circulation, (4) extravasation into the distant organ, and (5) survival and growth at the secondary site (hereafter defined as metastatic growth ). (frontiersin.org)
  • This is a rate-limiting step in metastasis because cells are often able to survive circulation and seed in distant organs, but are unable to proliferate into metastases ( 1 ). (frontiersin.org)
  • I studied the effect of this compound on FAK-IGF-1R protein interactions, when administered alone or in combination with 5-FU or gemcitabine chemotherapy on cell signaling, viability and apoptosis in human melanoma (A375, C8161, SK-Mel28), esophageal (KYSE 70, 140) and pancreatic (Miapaca-2, Panc-1) cancer cells and on in vivo tumor growth in xenograft mouse models. (ufl.edu)
  • The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells. (semanticscholar.org)
  • Transfection of J774A.1 macrophages with YopP induced a moderate, but significant degree of apoptosis (40-50% of transfected cells). (jimmunol.org)
  • Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a biosensor or integrator to control cell motility. (nih.gov)
  • Focal adhesion kinase (FAK) is thought to play a key role in maintaining focal adhesion function and cell survival, whereas caspase-mediated FAK proteolysis is implicated in focal adhesion disassembly during apoptosis. (portlandpress.com)
  • The targeting vector, pKO 4F2, consisted of a 1.6-kb 5′ homologous region, a 5-kb 3′ homologous region (Fig. 6 A , which is published as supporting information on the PNAS web site), and in the region of exon 1, encoding the transmembrane domain of CD98hc, was replaced with a neomycin selection cassette. (pnas.org)
  • Several years later DCC was shown to encode a transmembrane receptor protein that mediated the effects of netrin-1 on axon outgrowth. (wikipedia.org)
  • VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. (abnova.com)
  • The only FAK-associated PP1 isoform between 1 and 8h was PP1δ. (biochemj.org)
  • Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase that localizes to focal adhesions, sites of integrin engagement with the extracellular matrix ( 7 ). (aacrjournals.org)
  • The activity of the nonreceptor tyrosine kinase, focal adhesion kinase (FAK), is thought to contribute to this phenotype. (aacrjournals.org)
  • These studies show that FAK dephosphorylation and focal adhesion disassembly are very early events mediating the onset of staurosporine-induced endothelial cell apoptosis and are dissociated from FAK proteolysis. (portlandpress.com)
  • Endothelial cell-cell adhesion within the wall of the vasculature controls a range of physiological processes, such as growth, integrity and barrier function. (portlandpress.com)
  • Here, we summarise the current knowledge of the mechanisms controlling endothelial cell-cell adhesion in the developing and mature blood vasculature. (portlandpress.com)
  • Activated Tie2 increases endothelial cell survival, adhesion, and cell junction integrity, thereby stabilizing the vasculature. (bireme.br)
  • Focal adhesion formation and turnover has been used as a model system for understanding the mechanisms of cellular adhesion. (hindawi.com)
  • Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. (uniprot.org)
  • The importance of junctions and cell adhesion during morphogenesis was demonstrated by early experiments where VE-cadherin was deleted in the mouse, resulting in embryonic lethality due to defects in vascular patterning [ 5 , 6 ]. (portlandpress.com)
  • Furthermore, CD98hc is required for efficient adhesion-induced activation of Akt and Rac GTPase, major contributors to the integrin-dependent signals involved in cell survival and cell migration. (pnas.org)
  • A requirement for CD98hc in adhesion-induced activation of Akt and Rac GTPase accounted for the defects in cell survival ( 12 ) and cell migration ( 13 ). (pnas.org)
  • Focal adhesion kinase (FAK) is a broadly expressed tyrosine kinase implicated in cellular functions such as migration, growth and survival . (bvsalud.org)
  • These studies propose cell adhesion to FN may induce MMP-9 expression which finally facilitate cellular activities like migration, invasion. (scirp.org)
  • Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. (uniprot.org)
  • Has a role in growth factor- stimulated directional cell migration and adhesion. (uniprot.org)
  • Taken together, our results suggest that GPR56 in melanoma metastases inhibits ECM accumulation and adhesion, which contributes to its negative effects on metastatic growth. (frontiersin.org)
  • it specifically inhibits the transcription of both NF-kappa β and heat shock transcription factor 1 (HSF1) and simultaneously activates p53. (cancer.gov)
  • Thus, Rho-kinase appears to mediate signals from Rho and to induce the formation of stress fibers and focal adhesions. (sciencemag.org)
  • We identified that ROS production during L. amazonensis infection occurs upon engagement of Dectin-1, a C-type lectin receptor that signals via spleen tyrosine kinase (Syk) to induce ROS. (jimmunol.org)
  • 1999). Moreover, cell adhesion processes induce resistance to genotoxic agents (Fridman et al . (scielo.org.ar)
  • In the absence of netrin-1, DCC signaling has been shown to induce apoptosis. (wikipedia.org)
  • Both angiotensin II (Ang II) and mechanical stretch activate MAP kinases in cardiac myocytes. (pubmedcentralcanada.ca)
  • Focal adhesion kinase (Fak) has been implicated as a signaling molecule involved in the early response of cardiac myocytes to mechanical stress. (ahajournals.org)
  • 1,2 Although mechanical forces might directly trigger signaling mechanisms in cardiac myocytes, the mechanism by which they are sensed and converted to biochemical signals remains elusive. (ahajournals.org)
  • Focal adhesion kinase (FAK) has been shown to be activated in cardiac myocytes exposed to mechanical stress. (physiology.org)
  • We recently showed ( 12 , 39 ) that FAK activation by mechanical stress is accompanied by its aggregation at myofilaments, Z disks, and costameres, implying that this kinase might be directly activated by mechanical stress in cardiac myocytes. (physiology.org)