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focal adhesion kinase 1 (FADK 1, pp125FAK, protein-tyrosine kinase 2, PTK2, FAK, FAK1)

Function: - non-receptor protein-tyrosine kinase - implicated in signaling pathways involved in cell motility, proliferation & apoptosis - activated by tyrosine-phosphorylation in response to a) integrin clustering induced by cell adhesion or antibody cross-linking b) G-protein coupled receptor occupancy by ligands such as bombesin or lysophosphatidic acid c) LDL receptor occupancy d) adhesion of cell surface integrins to fibronectin - activated by integrin-beta 1, 2 or 3 cross-linking - associates integrin beta-1 through an N-terminal domain - plays a potential role in oncogenic transformations resulting in increased kinase activity - interacts with CAS family members & with GIT1, SORBS1 & BCAR3 - interacts with SHB (putative) - interacts with TGFB1I1 - phosphorylated on 6 Tyr upon activation - Tyr phosphorylation occurs via autophosphorylation (Y397) & perhaps phosphorylation by src (Y925) - Tyr-phosphtates provide binding sites for SH2 domains of src & Grb2, Csk & PI-3 kinase ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate Structure: - 1st pro-rich domain interacts with the SH3 domain of CRK-associated substrate (BCAR1) & CASL (putative) - carboxy-terminal region contains a focal adhesion targeting (FAT) domain which mediates the localization of FAK1 to focal adhesions - belongs to the protein kinase superfamily, Tyr protein kinase family, FAK subfamily - contains 1 FERM domain - contains 1 protein kinase domain Compartment: - cell junction, focal adhesion, cytoplasmic side - constituent of focal adhesions Alternative splicing: named isoforms=4 Expression: - expressed in all organs tested - expressed in lymphoid cell lines - most abundant in brain

General

cytoskeletal protein focal adhesion kinase (FAK)

Properties

SIZE: entity length = 1052 aa MW = 119 kD COMPARTMENT: cytoplasm MOTIF: FERM domain NAME: FERM domain SITE: 35-355 Tyr phosphorylation site {Y397} Tyr phosphorylation site {Y407} kinase domain SITE: 422-680 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 428-436 ATP-binding site NAME: ATP-binding site SITE: 454-454 aspartate residue {D546} Tyr phosphorylation site {Y576} Tyr phosphorylation site {Y577} FAT domain NAME: FAT domain SITE: 707-1052 MOTIF: Tyr phosphorylation site {Y861} binding site FOR-BINDING-OF: Paxillin proline-rich region SITE: 712-733 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S722} Ser phosphorylation site {S840} Ser phosphorylation site {S843} proline-rich region SITE: 863-913 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S910} Tyr phosphorylation site {Y925} STATE: active state

References

  1. Bolen JB, Rowley RB, Spana C, Tsygankov AY. The Src family of tyrosine protein kinases in hemopoietic signal transduction. FASEB J. 1992 Dec;6(15):3403-9. Review. PMID: 1281458
  2. Pawson T Protein modules and signalling networks Nature 373:573 1995 PMID: 7531822
  3. Clark EA & Brugge JS Integrins and signal transduction pathways: the road taken. Science 268:233 1995 PMID: 7716514
  4. UniProt :accession Q05397

Databases & Figures

OMIM 600758 UniProt Q05397 PFAM correlations KEGG correlations ENZYME 2.7.10.2 E-cadherin/CD31 ... F-actin