Focal Paxillin

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... 

Despite this complexity, most integrins share two, key interrelated functions first, to promote the assembly and organization of the actin cytoskeleton [122, 123] and second, to regulate signal transduction cascades [124-126], Spanning the cell membrane, these subunits serve as a communication pathway, linking the actin cytoskeleton and intracellular cytoplasmic proteins involved in focal adhesion complexes (FACs) with the cell s dynamic extracellular environment (Fig. 8) [127-130]. There are at least 50 distinct proteins known to be involved in FACs. Actin [131], vinculin, talin, tensin, a-actinin, and filamin provide a structural role, while focal adhesion kinase [132], integrin-linked kinase, Src-family kinase, PINCH, paxillin... 

Leduc, I., and Meloche, S. 1995. Angiotensin II stimulates tyrosine phosphorylation of the focal adhesion-associated protein paxillin in aortic smooth muscle cells. J Biol Chem 270 4401 1404. 

Endothelial cell migration is mediated by two additional pathways that stimulate cytoskeletal reorganization. These involve the p38 MAPK and focal adhesion kinase with paxillin phosphorylation, respectively [31]. PIP3 also activates the small GTP-binding protein Rac which facilitates endothelial cell migration. The PI3K pathway may also contribute to VEGF-enhanced endothelial cell proliferation [32],... 

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

Schaller MD, Otey CA, Hildebrand ID, Parsons JT. Focal adhe- 58. sion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J. Cell. Biol. 1995 130 1181-1187. 

Brown MC, Perrotta JA, Turner CE. Identification of LIM3 as 60. the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding. J. Cell. Biol. 61. 1996 135 1109-1123. 

Shen Y, Schneider G, Cloutier JE, Veillette A, Schaller MD. Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. J. Biol. Chem. 1998 273 6474—6781. Angers-Loustau A, Cote JE, Charest A, Dowbenko D, Spencer S, Lasky LA, Tremblay ML. Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and c)dokinesis in fibroblasts. J. Cell. Biol. 1999 144 1019-1031. 

Nikolopoulos SN, Turner CE. Actopaxin, a new focal adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion. J. Cell. Biol. 2000 151 1435-1448. 

Turner CE, Glenney JR Jr, Burridge K. Paxillin a new vinculin-binding protein present in focal adhesions. J. Cell. Biol. 1990 111 1059-1068. 

SCHALLER MD, OTEY CA, HEDEBRAND JD, Parsons JT. Focal adhesion kinase and paxillin bind to peptides mimicking Pintegrin cytoplasmic domains, y Cell frio/130 1181-1187,1995. 

Schaller, M.D., Otey, C.A., Hildebrand, J.D. and Parsons, J.T. (1995) Focal adhesion kinase and paxillin bind to peptides mimik-king beta integrin cytoplasmic domains. J.Cell Biol, 130, 1181-1187. 

Koukouritaki SB, Vardaki EA, Papakonstanti EA, Lianos E, Stournaras C, Emmanouel DS. TNPa induces actin cytoskeleton reorganization in glomerular epithelial cells involving tyrosine phosphorylation of paxillin and focal adhesion kinase. Mol... 

Wang X, Fukuda K et al (2008) The stmcture of alpha-parvin CH2-paxillin EDI complex reveals a novel modular recognition for focal adhesion assembly. J Biol Chem 283 (30) 21113-21119... 

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