Tyrosine kinaseProtein kinaseIntracellularRegulatesProteinsInhibitionPhosphorylationIntegrin effectorCytoplasmicEukaryotic proteinCytoskeletonMiceExtracellularPathwaysInhibitorPaxillinSignal TransductionTargetingFluorescenceRhoAVinculinAutosomal recessiveSubstrateInflammatoryActivationGenesLineageCellConcentrationStress FibersPathwayActivityDistinctMoleculeBiologicalDomainInteractionsHumanClassification
Tyrosine kinase5
- Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that regulates cell signaling, proliferation, migration, and development. (rcsb.org)
- Focal Adhesion Kinase (FAK) is a cytoplasmic tyrosine kinase that colocalizes with integrins in focal adhesions. (fishersci.com)
- Focal adhesion kinase (FAK) is a tyrosine kinase localized at the site of focal adhesions (FA). (aacrjournals.org)
- The focal adhesion kinase (FAK) is an intracellular tyrosine kinase associated with the regulation of cell growth, migration, and survival. (elsevierpure.com)
- A further 91 subfamilies were found in all three metazoan kinomes, including the tyrosine kinase (TK) group and the TKL group, which mediate much of the complexity of intercellular signal transduction. (wormbook.org)
Protein kinase9
- FAK signaling facilitated TNF-α-induced, mitogen-activated protein kinase activation, and, surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription factor required for TNF-α-induced VCAM-1 production. (escholarship.org)
- and protein kinase activity. (nih.gov)
- Orthologous to human MAPK1 (mitogen-activated protein kinase 1). (nih.gov)
- Transient activation of AMP-activated protein kinase at G1/S phase transition is required for control of S phase in NIH3T3 cells. (nih.gov)
- Most protein kinases share a common ePK (eukaryotic protein kinase) catalytic domain, and can be identified by sequence similarity with Blast or profile hidden Markov models (HMMs). (wormbook.org)
- We identified 438 protein kinase genes, including 20 atypical kinases, and an additional 25 kinase fragments or pseudogenes. (wormbook.org)
- The RAC serine/threonine-protein kinase (AKT) family of serine/threonine protein kinases, particularly the AKT1 isoform, has been identified abnormally expressed in hepatocellular carcinoma (HCC) cells, and is highly associated with cell behavior, including proliferation, survival, metabolism, and tumorigenesis. (spandidos-publications.com)
- The phosphoinositide 3-kinase (PI3K)/RAC seine/threonine-protein kinase (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is a promising therapeutic target owing to its frequent dysregulation in HCC and the critical functions it has in regulating cell survival, proliferation, apoptosis, migration and angiogenesis through phosphorylation of distinct protein substrates ( 6 , 7 ). (spandidos-publications.com)
- Increased adhesion of the cancer cells depended on activation of cyclooxygenase-2, an enzyme that is involved in progression of colon cancers, whereas adhesion of the intestinal epithelial cells was augmented by LTD4-induced translocation of protein kinase C to areas where integrins bind to matrix proteins (focal adhesions). (lu.se)
Intracellular3
- 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)
- Adhesion stress, including that caused by deletion of FAK, promotes selective sequestration of active Src away from integrin adhesions and into intracellular autophagic structures and on for lysosomal degradation. (ncri.org.uk)
- Mechanistic studies showed that MWCNTs induced fibrogenesis of NHLFs through promoting expression and phosphorylation of focal adhesion kinase (FAK), while attenuating intracellular tension in the cells on stiff gels could increase MWCNTs uptake and thus elevate the induced fibrogenic responses. (cdc.gov)
Regulates2
- Using a synthetic model of the provisional matrix, we have found that tenascin-C regulates cell responses to a fibrin-FN matrix through modulation of focal adhesion kinase (FAK) and RhoA activation. (ox.ac.uk)
- Integrin-mediated adhesion to extracellular matrix regulates the migration and proliferation of many cell types, but its role in glioma progression is undefined. (elsevierpure.com)
Proteins5
- 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)
- Proteins Secreted by Lung Cancer Cells Induce the Onset of Proteinuria via Focal Adhesion Kinase Signaling in Mice. (bvsalud.org)
- By phosphorylating substrate proteins, kinases modify the activity, location and affinities of up to 30% of all cellular proteins, and direct most cellular processes, particularly in signal transduction and co-ordination of complex pathways. (wormbook.org)
- Binding of viral proteins to their ligands activates signaling pathways-focal adhesion kinase for human herpesvirus 8, JAK1, tyk2 and STAT1/2 for West Nile virus (WNV), I κ B-kinase, and nuclear transcription factor κ B (NF-κB) for influenza virus-resulting in virus entry, DNA delivery to nucleus, and modulation of protein expression that stimulate or inhibit virus replication. (cdc.gov)
- In general, cell adhesion favours cell survival signalling, and integrins are the main receptors responsible for mediating the attachment of different types of cells to matrix proteins. (lu.se)
Inhibition3
- Inhibition of cell/substrate adhesion with specific anti-integrin antibodies demonstrated that P-FAKSer732 activation is not induced by integrin clustering. (aacrjournals.org)
- Inhibition of autophagy leads to cancer cell death, demonstrating that selective autophagic targeting of Src (and other oncogenic tyrosine kinases) is an adaptive mechanism to maintain viability, identifying a cancer cell vulnerability that provides a new therapeutic opportunity. (ncri.org.uk)
- Morphological rescue is possible following Rho kinase inhibition in an oligodendrocyte subset. (jneurosci.org)
Phosphorylation5
- 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)
- 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)
- Kinases are enzymes that catalyze reactions of phosphorylation. (wikipedia.org)
- Unlike other cyclin-dependent kinases, CDK5 does not also require phosphorylation on the T loop. (wikipedia.org)
Integrin effector2
- Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. (cardiff.ac.uk)
- Focal Adhesion Kinase (FAK) is a Src-regulated, integrin-effector kinase that is frequently elevated in cancer, and there are a number of small molecule FAK inhibitors currently in clinical development. (ncri.org.uk)
Cytoplasmic2
- FAK seems also to have a role in the proliferation of tumor cells by its biochemical and biological association to cytoplasmic kinases such as src and ERK. (aacrjournals.org)
- We investigated the role of the cytoplasmic tyrosine kinases FAK and Pyk2, potential integrin effectors, in the phenotypic determination of four different human glioblastoma cell lines. (elsevierpure.com)
Eukaryotic protein1
- Cdk5 belongs to the eukaryotic protein kinases (ePKs). (wikipedia.org)
Cytoskeleton6
- Focal adhesion kinase (FAK) is a key integrator of integrin-mediated signals from the extracellular matrix to the cytoskeleton and downstream signaling molecules. (techscience.com)
- Although previous studies have identified different chemotropic and adhesion molecules that influence axonal development, the molecular mechanism by which these signals control the cytoskeleton remains poorly understood. (biologists.com)
- ILK forms an obligate heterotrimeric complex with particularly interesting Cys-His-rich protein (PINCH) and parvin, which together lend stability to the actin cytoskeleton at focal adhesions ( Brakebusch and Fässler, 2003 ). (jneurosci.org)
- I suggest that in the context of semaphorin 3A signaling, RhoA-kinase serves as a switch to change the function of the F-actin cytoskeleton from promoting protrusive activity to generating contractile forces. (biologists.com)
- Similarly, depletion of either Rasip1 or Arhgap29 in cultured ECs blocks in vitro lumen formation, fundamentally alters the cytoskeleton, and reduces integrin-dependent adhesion to ECM . (xenbase.org)
- This thesis is focused primarily on the effect that LTD4 has on reorganisation of the actin cytoskeleton and on cell-cell and cell-matrix adhesion properties. (lu.se)
Mice1
- Importantly, cancer cell immune evasion depends on FAK's catalytic activity, and VS-4718, a small molecule FAK kinase inhibitor that is in clinical development, suppresses regulatory T-cells, increases cytotoxic CD8 + T-cells and promotes tumour regression and clearance in mice. (ncri.org.uk)
Extracellular2
- Upon cell adhesion to the extracellular matrix, FAK is being translocated toward focal adhesion sites and activated. (rcsb.org)
- Rasipl null angioblasts fail to properly localize the polarity determinant Par3 and display defective cell polarity, resulting in mislocalized junctional complexes and loss of adhesion to extracellular matrix ( ECM ). (xenbase.org)
Pathways5
- Of the pathways evaluated, we found that focal adhesion kinase (FAK) activity is elevated in human PDAC and that FAK activity correlates with highly fibrotic tumors with poor CD8 + T cell infiltration. (biomedcentral.com)
- Tenascin-C modulates matrix contraction via focal adhesion kinase- and Rho-mediated signaling pathways. (ox.ac.uk)
- Recently Cdk5 has emerged as an essential kinase in sensory pathways. (wikipedia.org)
- Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. (wormbook.org)
- Many of these pathways are highly conserved, and 53 distinct kinase functions and subfamilies appear to have been conserved between yeasts, nematodes, insects and vertebrates, with a further 91 subfamilies of kinases being seen throughout metazoan genomes. (wormbook.org)
Inhibitor1
- The oral FAK kinase inhibitor VS-4718, currently in Phase I clinical evaluation, was tested to determine if it could overcome the immunosuppressive tumor microenvironment of PDAC. (biomedcentral.com)
Paxillin1
- These complexes, which are associated with lamellipodia and filopodia, contain vinculin, paxillin, and focal adhesion kinase, but are distinct from and formed independently of rho-induced focal adhesions. (nih.gov)
Signal Transduction1
- Focal adhesion kinase (FAK) and CD4 fulfil vital functions in cellular signal transduction: FAK is a central component in integrin signalling, whereas CD4 plays essential roles in the immune defence. (edu.sa)
Targeting2
- This cellular localization is directed by a 125 amino acid sequence at the C-terminus called the "Focal Adhesion Targeting" sequence (FAT). (fishersci.com)
- Using crystallography and microcalorimetry, we here show that the focal adhesion targeting (FAT) domain of FAK binds specifically to the CD4 endocytosis motif in vitro. (edu.sa)
Fluorescence1
- Recent fluorescence resonance energy transfer experiments revealed a closure of the FERM-kinase interface upon ATP binding, which is reversed upon additional binding of PIP₂. (rcsb.org)
RhoA3
- I investigated the roles of RhoA-kinase and myosin II in semaphorin-3A-induced growth cone collapse and axon retraction. (biologists.com)
- Formation of axonal F-actin bundles was independent of myosin II, but partially required RhoA-kinase activity. (biologists.com)
- Conversely, RhoA-kinase activity was required to shut down F-actin polymerization underlying protrusive activity. (biologists.com)
Vinculin1
Autosomal recessive1
- Creatine kinase is also used for diagnosis because autosomal recessive LGMDs often cause extremely high CK levels. (medscape.com)
Substrate2
- 202:849) controlling cell-substrate adhesion. (ucsf.edu)
- Thaw the Active FAK, Kinase Assay Buffer III (5X), and Substrate on ice. (rndsystems.com)
Inflammatory3
- Tumor necrosis factor-α (TNF-α) and focal adhesion kinase (FAK) are key regulators of inflammatory and integrin-matrix signaling, respectively. (escholarship.org)
- These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover. (escholarship.org)
- Integrin - focal adhesion kinase (FAK) signaling and inflammatory responses were evaluated in podocytes either exposed to soluble LCSePs or seeded onto substrates with immobilized LCSePs. (bvsalud.org)
Activation2
- We identified a network of mainly charged residue-residue interactions spanning from the PIP₂ binding site to the distant interface between the kinase and FERM domains, comprising candidate residues for mutagenesis to validate the predicted mechanism of FAK activation. (rcsb.org)
- The rac1 target p21-activated kinase translocated from a cytosolic to a cytoskeletal distribution, suggesting that rac1 activation was inducing focal adhesion reorganization. (jci.org)
Genes2
- Such radiations include genes involved in spermatogenesis, chemosensation, Wnt signaling and FGF receptor-like kinases. (wormbook.org)
- Protein kinases constitute one of the largest and most important of protein families, accounting for ~2% of genes in a variety of eukaryotic genomes. (wormbook.org)
Lineage1
- The gain and loss of kinase functions and subfamilies in each evolutionary lineage is also seen. (wormbook.org)
Cell8
- Vascular cell adhesion molecule-1 (VCAM-1) plays important roles in development and inflammation. (escholarship.org)
- Cells on fibrin-FN+tenascin-C redistribute their actin to the cell cortex, downregulate focal adhesion formation, and do not assemble a FN matrix. (ox.ac.uk)
- Phosphorylations are of vital importance during glycolysis, therefore, making kinases an essential part of the cell due to their role in the metabolism, cell signaling, and many other processes. (wikipedia.org)
- Cdk5 is a proline-directed serine/threonine kinase, which was first identified as a CDK family member due to its similar structure to CDC2/CDK1 in humans, a protein that plays a crucial role in the regulation of the cell cycle. (wikipedia.org)
- We speculated that focal adhesion kinase (FAK) might play a critical role in the TNFα-induced cell death. (elsevierpure.com)
- This makes kinase signaling particularly amenable to comparative studies, and kinase activity a particularly good readout of the physiological state of any cell. (wormbook.org)
- In 2003, Lamartine reclassified the ectodermal dysplasias into the following 4 functional groups based on the underlying pathophysiologic defect: (1) cell-to-cell communication and signaling, (2) adhesion, (3) development, and (4) other. (medscape.com)
- [ 8 ] Other classification systems categorize the ectodermal dysplasias based on defects in cell-cell communication and signaling, adhesion, transcription regulation, or development. (medscape.com)
Concentration1
- Prepare a 15 μL enzyme dilution with Kinase Dilution Buffer X (1X) at the desired concentration, with Kinase Dilution Buffer X (1X), in a pre-chilled 96-well plate. (rndsystems.com)
Stress Fibers1
- In addition to stress fibers, rho controls the assembly of focal adhesion complexes. (nih.gov)
Pathway1
- DEGs were also enriched in human papillomavirus infections, the focal adhesion pathway, PI3K-Akt signaling pathway, and among others. (hindawi.com)
Activity1
- Determine the corrected activity (RLU) by removing the blank control value (see step 4) for each sample and calculate the kinase specific activity as outlined below. (rndsystems.com)
Distinct1
- Since kinases perform such a variety of distinct basic cellular functions, it is not surprising to see that 53 subfamilies and functions are present in all four kinomes ( Figure 1 ). (wormbook.org)
Molecule1
- The molecule belongs to the cyclin-dependent kinase family. (wikipedia.org)
Biological2
- We use genetic and chemical intervention and imaging to understand the biological and molecular mechanisms by which adhesion-linked tyrosine kinases promote malignancy, and how best to perturb for therapeutic advantage. (ncri.org.uk)
- The classification is based on sequence similarity within the kinase domain, the presence of additional domains, known biological functions, and conservation across divergent genomes. (wormbook.org)
Domain1
- ILK is composed of three domains, an N-terminal ankryin domain, a pleckstrin homology domain, and a putative kinase domain. (jneurosci.org)
Interactions1
- When podocytes were stimulated by immobilized LCSePs, FAK accumulated at focal adhesions , synaptopodin dissociated from F-actin , and disrupting the interactions between synaptopodin and α- actinin was observed. (bvsalud.org)
Human4
- Kinases are deeply conserved in evolution, and the worm has family homologs for over 80% of the human kinome. (wormbook.org)
- To put worm kinases into an evolutionary and functional context, we compared them with the distant kinomes of human, fly, and yeast. (wormbook.org)
- Distribution of 212 kinase subfamilies throughout four kinomes: the yeast Saccharomyces cerevisiae , the nematode worm Caenorhabditis elegans , the fruit fly Drosophila melanogaster and human. (wormbook.org)
- Nematodes share 153 subfamilies with human, providing close homologs for 81% (419/518) of all human kinases. (wormbook.org)
Classification1
- The classification of each worm kinase is given in Appendix A. (wormbook.org)