2l6h

Structural highlights

Function

FAK1_CHICK 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, 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), ephrin receptors, netrin receptors 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 activation of 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. Regulates P53/TP53 activity and stability. Phosphorylates SRC; this increases SRC kinase activity. Isoform 2 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling.^{[1] [2] [3] [4] [5] [6]} PAXI_CHICK Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Binds in vitro to vinculin as well as to the SH3 domain of c-SRC and, when tyrosine phosphorylated, to the SH2 domain of v-CRK.

See Also

• Focal adhesion kinase 3D structures

References

1. ↑ Ren XR, Ming GL, Xie Y, Hong Y, Sun DM, Zhao ZQ, Feng Z, Wang Q, Shim S, Chen ZF, Song HJ, Mei L, Xiong WC. Focal adhesion kinase in netrin-1 signaling. Nat Neurosci. 2004 Nov;7(11):1204-12. Epub 2004 Oct 17. PMID:15494733 doi:10.1038/nn1330
2. ↑ Li W, Lee J, Vikis HG, Lee SH, Liu G, Aurandt J, Shen TL, Fearon ER, Guan JL, Han M, Rao Y, Hong K, Guan KL. Activation of FAK and Src are receptor-proximal events required for netrin signaling. Nat Neurosci. 2004 Nov;7(11):1213-21. Epub 2004 Oct 17. PMID:15494734 doi:10.1038/nn1329
3. ↑ Liu G, Beggs H, Jurgensen C, Park HT, Tang H, Gorski J, Jones KR, Reichardt LF, Wu J, Rao Y. Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction. Nat Neurosci. 2004 Nov;7(11):1222-32. Epub 2004 Oct 17. PMID:15494732 doi:10.1038/nn1331
4. ↑ Koshman YE, Kim T, Chu M, Engman SJ, Iyengar R, Robia SL, Samarel AM. FRNK inhibition of focal adhesion kinase-dependent signaling and migration in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2226-33. doi:, 10.1161/ATVBAHA.110.212761. Epub 2010 Aug 12. PMID:20705914 doi:10.1161/ATVBAHA.110.212761
5. ↑ Koshman YE, Chu M, Engman SJ, Kim T, Iyengar R, Robia SL, Samarel AM. Focal adhesion kinase-related nonkinase inhibits vascular smooth muscle cell invasion by focal adhesion targeting, tyrosine 168 phosphorylation, and competition for p130(Cas) binding. Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2432-40. doi:, 10.1161/ATVBAHA.111.235549. PMID:21852560 doi:10.1161/ATVBAHA.111.235549
6. ↑ Chu M, Iyengar R, Koshman YE, Kim T, Russell B, Martin JL, Heroux AL, Robia SL, Samarel AM. Serine-910 phosphorylation of focal adhesion kinase is critical for sarcomere reorganization in cardiomyocyte hypertrophy. Cardiovasc Res. 2011 Dec 1;92(3):409-19. doi: 10.1093/cvr/cvr247. Epub 2011 Sep, 21. PMID:21937583 doi:10.1093/cvr/cvr247