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- _4 value "Regulation of cell migration appears to implicate a cross talk with Rhofamily proteins. In migrating cells, PKB/Akt localizes to the leading edge [79], a site of high Rac activity [80]. In endothelial cells PKB/Akt has been reported to be both upstream and downstream of Rac and Cdc42 [81-83]. Endothelial cell migration induced by VEGFR2- stimulation involves integrin activation via a PI-3K and PKB/Akt-dependent signaling pathway [84]. Rho family GTPases. The small GTPases Rho, Rac and Cdc42 participate in the regulation of actin polymerization necessary for the formation of stress fibers, focal adhesions, lamellipodia and filopodia [85], and modulate cell proliferation and gene expression [86,87]. Integrin ligation activates Rho proteins by promoting GTP loading and translocation from the cytosol to the membrane [88]. Rac activity is essential for endothelial cell migration and angiogenesis [89,90] and this effect requires the Rac effector protein p21 activated kinase 1 (PAK1). Inhibition of Rac or PAK1 function by dominant negative constructs in endothelial cells in vivo inhibits growth factor-induced angiogenesis [90,91]." provenance.
- _4 wasQuotedFrom 14984767 provenance.