DOCK-GEFs:RAC1, CDC42 DOCK-GEFs RAC1, CDC42 DOCKs bind to RhoGEFs Authored: Ouwehand, WH, 2010-11-12 Edited: Jupe, S, 2010-11-12 Members of the Dedicator of cytokinesis (DOCK) family, also known as the Dock180 superfamily, are Rho GTPase guanine nucleotide exchange factors (GEFs), modulating Rho GTPase activity (Cote & Vuori 2002). All eleven human members share the presence of two evolutionarily conserved protein domains, termed DHR-1 and DHR-2 (Cote & Vuori 2007). The DHR-2 domains of several DOCKs interact with the nucleotide-free forms of Rho GTPases, intermediates in the catalytic reaction leading to the exchange of GDP for GTP. DHR-2 domains have been shown necessary and sufficient to promote specific guanine nucleotide exchange on various Rho GTPases, both in vitro and in vivo. Inactivation of the DHR-2 domain in DOCK1 (Dock180) has been shown to block Rac activation, cell migration and phagocytosis (Brugnera et al. 2002, Grimsley et al. 2004, Cote & Vuori 2002). The DHR-1 domain of DOCK1 was shown to mediate a specific interaction with PIP2 and PIP3 signaling lipids in vitro and in cells (Cote et al. 2005). Mutations of the DOCK1 DHR-1 domain blocked Rac-dependent cell elongation and cell migration suggesting that the role of DHR-1 is to position DOCK1 at sites of PIP3 production by PI3-kinase, coupling this to Rac signaling (Cote & Vuori 2007). Pubmed12134158 Pubmed12432077 Pubmed14638695 Pubmed15247287 Pubmed15710388 Pubmed16025104 Pubmed17027967 Pubmed17196961 Pubmed17765544 Reactome Database ID Release 431011598 Reactome, http://www.reactome.org ReactomeREACT_25140 Reviewed: Akkerman, JW, 2010-10-29