Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T15068
|
||||
Former ID |
TTDR00669
|
||||
Target Name |
Focal adhesion kinase
|
||||
Gene Name |
PTK2
|
||||
Synonyms |
FADK; FAK; Protein-tyrosine kinase 2; PTK2
|
||||
Target Type |
Clinical Trial
|
||||
Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
Late-stage solid tumors [ICD9: 140-199, 210-229; ICD10: C00-C75, C7A, C7B, D10-D36, D3A] | |||||
Mesothelioma [ICD9: 163; ICD10: C45] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
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. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrinreceptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activationof MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; 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. Promotes phosphorylation ofBCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
|
||||
BioChemical Class |
Kinase
|
||||
Target Validation |
T15068
|
||||
UniProt ID | |||||
EC Number |
EC 2.7.10.2
|
||||
Sequence |
MAAAYLDPNLNHTPNSSTKTHLGTGMERSPGAMERVLKVFHYFESNSEPTTWASIIRHGD
ATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEW KYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMLEIADQVDQEIALKLGCLEIRRSY WEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESI LKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNPTHLADFTQVQ TIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGTSQSFII RPQKEGERALPSIPKLANSEKQGMRTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRE RIELGRCIGEGQFGDVHQGIYMSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDH PHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESK RFVHRDIAARNVLVSSNDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFT SASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWA YDPSRRPRFTELKAQLSTILEEEKAQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGY PSPRSSEGFYPSPQHMVQTNHYQVSGYPGSHGITAMAGSIYPGQASLLDQTDSWNHRPQE IAMWQPNVEDSTVLDLRGIGQVLPTHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLS RGSIDREDGSLQGPIGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLGSLASLSSPADSYNE GVKLQPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLA LRTLLATVDETIPLLPASTHREIEMAQKLLNSDLGELINKMKLAQQYVMTSLQQEYKKQM LTAAHALAVDAKNLLDVIDQARLKMLGQTRPH |
||||
Drugs and Mode of Action | |||||
Drug(s) | VS-6063 | Drug Info | Phase 2 | Mesothelioma | [524313] |
BI-853520 | Drug Info | Phase 1 | Solid tumours | [524377] | |
CEP-37440 | Drug Info | Phase 1 | Late-stage solid tumors | [524397] | |
GSK-2256098 | Drug Info | Phase 1 | Cancer | [542854], [548997] | |
PF-4554878 | Drug Info | Phase 1 | Cancer | [522477], [542833] | |
PF-562271 | Drug Info | Phase 1 | Solid tumours | [522306] | |
VS-4718 | Drug Info | Phase 1 | Solid tumours | [524282] | |
Modulator | BI-853520 | Drug Info | [1572591] | ||
CEP-37440 | Drug Info | [1572591] | |||
Inhibitor | BMS-536924 | Drug Info | [527711] | ||
compound 30 | Drug Info | [532236] | |||
GSK-2256098 | Drug Info | [533062] | |||
PF-228 | Drug Info | [528764] | |||
PF-4554878 | Drug Info | [549761] | |||
PF-562271 | Drug Info | [531618] | |||
PND-1186 | Drug Info | [543569] | |||
VS-4718 | Drug Info | [532800] | |||
VS-6063 | Drug Info | [532487] | |||
Pathways | |||||
KEGG Pathway | ErbB signaling pathway | ||||
Chemokine signaling pathway | |||||
PI3K-Akt signaling pathway | |||||
Axon guidance | |||||
VEGF signaling pathway | |||||
Focal adhesion | |||||
Leukocyte transendothelial migration | |||||
Regulation of actin cytoskeleton | |||||
Bacterial invasion of epithelial cells | |||||
Amoebiasis | |||||
Pathways in cancer | |||||
Transcriptional misregulation in cancer | |||||
Proteoglycans in cancer | |||||
Small cell lung cancer | |||||
PANTHER Pathway | Angiogenesis | ||||
Integrin signalling pathway | |||||
VEGF signaling pathway | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | LPA receptor mediated events | ||||
CXCR4-mediated signaling events | |||||
Reactome | Apoptotic cleavage of cellular proteins | ||||
Regulation of actin dynamics for phagocytic cup formation | |||||
Integrin alphaIIb beta3 signaling | |||||
SOS provides linkage to MAPK signaling for Integrins | |||||
p130Cas linkage to MAPK signaling for integrins | |||||
NCAM signaling for neurite out-growth | |||||
Signal regulatory protein (SIRP) family interactions | |||||
EPHB-mediated forward signaling | |||||
EPHA-mediated growth cone collapse | |||||
DCC mediated attractive signaling | |||||
Netrin mediated repulsion signals | |||||
VEGFA-VEGFR2 Pathway | |||||
RHO GTPases Activate WASPs and WAVEs | |||||
RAF/MAP kinase cascade | |||||
WikiPathways | Regulation of Actin Cytoskeleton | ||||
EGF/EGFR Signaling Pathway | |||||
TGF beta Signaling Pathway | |||||
Signaling of Hepatocyte Growth Factor Receptor | |||||
Focal Adhesion | |||||
Apoptosis-related network due to altered Notch3 in ovarian cancer | |||||
Nanoparticle-mediated activation of receptor signaling | |||||
JAK/STAT | |||||
Primary Focal Segmental Glomerulosclerosis FSGS | |||||
Alpha 6 Beta 4 signaling pathway | |||||
Corticotropin-releasing hormone | |||||
Leptin signaling pathway | |||||
RANKL/RANK Signaling Pathway | |||||
Netrin-1 signaling | |||||
NCAM signaling for neurite out-growth | |||||
Integrin-mediated Cell Adhesion | |||||
Integrin alphaIIb beta3 signaling | |||||
Apoptotic execution phase | |||||
Angiogenesis | |||||
Androgen receptor signaling pathway | |||||
References | |||||
Ref 522306 | ClinicalTrials.gov (NCT00666926) Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms. U.S. National Institutes of Health. | ||||
Ref 522477 | ClinicalTrials.gov (NCT00787033) A Study Of PF-04554878 In Patients With Advanced Non-Hematologic Malignancies. U.S. National Institutes of Health. | ||||
Ref 524282 | ClinicalTrials.gov (NCT01849744) Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies. U.S. National Institutes of Health. | ||||
Ref 524313 | ClinicalTrials.gov (NCT01870609) Placebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma. U.S. National Institutes of Health. | ||||
Ref 524377 | ClinicalTrials.gov (NCT01905111) A Study of BI 853520 in Japanese and Taiwanese Patients With Various Types of Advanced or Metastatic Cancer. U.S. National Institutes of Health. | ||||
Ref 524397 | ClinicalTrials.gov (NCT01922752) To Determine the Maximum Tolerated Dose of Oral CEP-37440 in Patients With Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health. | ||||
Ref 542833 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7910). | ||||
Ref 527711 | J Med Chem. 2005 Sep 8;48(18):5639-43.Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. | ||||
Ref 528764 | J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar 28.Cellular characterization of a novel focal adhesion kinase inhibitor. | ||||
Ref 531618 | Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45. | ||||
Ref 532236 | Structure-based discovery of cellular-active allosteric inhibitors of FAK. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1779-85. | ||||
Ref 532487 | Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. | ||||
Ref 532800 | FAK Inhibition disrupts a beta5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth. Mol Cancer Ther. 2014 Aug;13(8):2050-61. | ||||
Ref 533062 | A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9. | ||||
Ref 543569 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2180). |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.