Fig. 2.

Schematic diagram of Pak activation by the small GTPases Rac and Cdc42. Signals from receptor tyrosine kinases, (e.g. insulin, EGF, PDGF, and VEGF receptors) and G protein-coupled receptors lead to activation of Pak via GTP-bound Rac and Cdc42. Activated Pak in turn initiates signaling cascades that culminate in the cellular response. In addition, activated Pak potentiates activation of the MAP kinase pathway. Of note, while activation of Pak via Rac and Cdc42 is well characterized, a number of GTPase-independent mechanisms for Pak activation have also been identified. GPCR, G protein-coupled receptors; RTK, receptor tyrosine kinase; PI3 K, phosphatidylinositol-3 kinase; PIP3, phosphatidylinositol (3, 4, 5) trisphosphate