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
  • integrin clustering induced by cell adhesion or antibody cross-linking
  • G-protein coupled receptor occupancy by ligands such as bombesin or lysophosphatidic acid
  • LDL receptor occupancy
  • 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

More general terms

• focal adhesion kinase (FAK)
• cytoskeletal protein

Database

• UniProt: http://www.uniprot.org/uniprot/Q05397.html
• OMIM: https://mirror.omim.org/entry/600758