RhoGAP, p190B (Rho GTPase-activating protein 5) from MyBioSource.com

The Rho family of GTPases, including Rho, Rac and Cdc42, are key regulators of diverse biological processes such as cytoskelatal organization, cell growth and differentiation, transciptional regulation, and cell adhesion/motility (1,2). The activities of these proteins are controlled by GTP binding such that in the GTP-bound state they are active, and in the GDP-bound state they become inactive. Three classes of regulatory proteins control the activity of the GTPases by balancing the levels of GTP/GDP binding: the guanine nucleotide exchange factors (GEFs), which promote the active state by facilitating the exchange of GDP for GTP; the guanine nucleotide dissociation inhibitors GDIs), which sequester the GDP-bound forms and may regulate their intracellular localization; and the GTPase activating proteins (GAPs), which increase GTP hydrolysis to promote the inactive state. The p190 RhoGAP familyconsists of two related proteins, p190-A and p190-B, which are both widely expressed and contain an amino terminal GTPase domain and a carboxy-terminal RhoGAP catalytic domain. Mice lacking p190-B RhoGAP show excessive Rho activation and a reduction in activation of the transcription factor CREB (3. Phenotypes of these mice are similar to those of CREB knockouts, with reduced cell size, as well as defects in thymus and neural development (3). Cells deficient in p190-B are also defective for adipogenesis, suggesting this pathway is critical for the adipogenesis-myogeneis switch." (4). There is increasing evidence that p190 undergoes tyrosine phosphorylation, which activates its GAP domain (4-6). Levels of tyrosine phosphorylation are enhanced by Src overexpression (5,6). IGF-1 treament downregulates Rho through phosphorylation and activation of p190-BRhoGAP, thereby enhancing IGF signaling implicated in adipogenesis (4)