DOCKs bind to RhoGEFs

Stable Identifier
R-HSA-1011598
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

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).

Literature References
PubMed ID Title Journal Year
17196961 Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth

Miyamoto, Y, Yamauchi, J, Sanbe, A, Tanoue, A

Exp Cell Res 2007
15247287 The novel Cdc42 guanine nucleotide exchange factor, zizimin1, dimerizes via the Cdc42-binding CZH2 domain

Meller, N, Irani-Tehrani, M, Ratnikov, BI, Paschal, BM, Schwartz, MA

J Biol Chem 2004
17027967 Dock4 is regulated by RhoG and promotes Rac-dependent cell migration

Hiramoto, K, Negishi, M, Katoh, H

Exp Cell Res 2006
12134158 Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex

Brugnera, E, Haney, L, Grimsley, C, Lu, M, Walk, SF, Tosello-Trampont, AC, Macara, IG, Madhani, H, Fink, GR, Ravichandran, KS

Nat Cell Biol 2002
15710388 Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes

Nishikimi, A, Meller, N, Uekawa, N, Isobe, K, Schwartz, MA, Maruyama, M

FEBS Lett 2005
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