Adhesions, focal

Adaptor protein, containing one SH2 and two SH3 domains, which assembles signaling complexes at receptors and focal adhesions. 

FAT Focal adhesion targeting domain Binding to focal adhesions complexes... 

Among the substrates of Src are other nonreceptor PTKs (e.g., Fak, Syk, and Tec kinases), RTKs (e.g. EGF and PDGF receptors), phospholipase Cy, PI3-kinase, phosphatases (e.g., SHP-2 and PP2A), and adaptor (e.g., She and Cbl) as well as focal adhesion proteins (e.g., paxillin, pl30Cas andtensin). Src-mediated phosphorylation either modulates enzymatic activity of... 

Fak (focal adhesion kinase) is expressed in most tissues and is evolutionary conserved across species. It is activated by integrin clustering and by stimulation of several G protein-coupled recqrtors and RTKs. Fak is associated with focal adhesions and regulates cell spreading and migration. The kinase is essential for embryonic development since the homozygote Fak knockout is embryonic lethal. Pyk2 (proline-rich tyrosine kinase 2), the second member of the Fak kinase family has a more restricted expression pattern (primarily neuronal and hematopoietic cells) and does not localize to focal adhesions. 

Burridge, K., Path, K., Kelly, T., Nuckolls, G., Turner, C. (1988). Focal adhesions Transmembrane junctions between the extracellular matrix and the cytoskeleton. Ann. Rev. Cell Biol. 4,487-525. Cleveland, D.W. Sullivan, K.F. (1985). Molecular biology and genetics of tubulin. Ann. Rev. Biochem. 54,331-365. 

Dunlevy, J.R., Couchman. J.R. (1993). Controlled induction of focal adhesion disassembly and migration in primary fibroblasts. J. Cell Sci. 105,489-500. 

Ridley, A.J., Hall, A. (1992). The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70,389-399. 

Cicala C, Arthos J, Ruiz M, et al. Induction of phosphorylation and intracellular association of CC chemokine receptor 5 and focal adhesion kinase in primary human CD4+ T cells by macrophage-tropic HIV envelope. J Immunol 1999 163(l) 420-426. 

Cicala C, Arthos J, Rubbert A, et al. HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells. Proc Natl Acad Sci U S A 2000 97(3) 1178-1183. 

Integrins present in focal adhesion complexes cause the recruitment of two types of protein tyrosine kinases to the plasma membrane focal adhesion kinase (FAK) and Src. They play a role in cell survival and proliferation. 

FIGURE 7-3 Integrins are heterodimers. Integrins consist of a and 3 subunits noncovalently linked, which interact via their cytoplasmic domains with a number of cytoplasmic proteins. The axpi integrin complex on the left binds to a complex which includes focal adhesion kinase (FAK). The a6P4 integrin complex contains fibronectin (FN) III repeats, which mediate binding to intermediate filaments. 

Protein kinase Cd, Akt kinase, calcium/calmodulin-dependent protein kinase IV, mitogen-activated protein kinase kinase (MEKK-1), focal adhesion kinase (FAK), protein phosphatase (PP)2A, calcineurin... 

Govindarajan G, EbleDM, Lucchesi PA, Samarel AM 2000 Focal adhesion kinase is involved in angiotensin Il-mediated protein synthesis in cultured vascular smooth muscle cells. Circ Res... 

Buhl, A.M., Johnson, N.L., Dhanasekaran, N. and Johnson, G.L., 1995, Ga and Gai3 stimulate Rho-dependent stress fibre formation and focal adhesion assembly, J. Biol. Chem. 270 24631-24634. 

Wang, F., Nobes, C.D., HaU, A. and Spiegel, S., 1997, Sphingosine 1-phosphate stimulates Rho-mediated tyrosine phosphorylation of focal adhesion kinase and paxiUin in Swiss 3T5 fibroblasts. Biochem. J. 324 481-488. 

Tamura, M., Gu, J., Danen, E.H., Takino, T., Miyamoto, S., Yamada, KM., 1999, PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidyhnositol 3-kinase/Akt cell survival pathway. JBiol Chem 274 ... 

---