Reactome | DOCKs bind to RhoGEFs

DOCKs bind to RhoGEFs

Stable Identifier

R-HSA-1011598

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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
15247287	The novel Cdc42 guanine nucleotide exchange factor, zizimin1, dimerizes via the Cdc42-binding CZH2 domain Meller, N, Ratnikov, BI, Schwartz, MA, Irani-Tehrani, M, Paschal, BM	J Biol Chem	2004
17196961	Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth Miyamoto, Y, Tanoue, A, Sanbe, A, Yamauchi, J	Exp Cell Res	2007
17027967	Dock4 is regulated by RhoG and promotes Rac-dependent cell migration Hiramoto, K, Katoh, H, Negishi, M	Exp Cell Res	2006
12134158	Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex Macara, IG, Walk, SF, Lu, M, Grimsley, C, Madhani, H, Fink, GR, Brugnera, E, Tosello-Trampont, AC, Ravichandran, KS, Haney, L	Nat Cell Biol	2002
15710388	Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes Meller, N, Schwartz, MA, Maruyama, M, Nishikimi, A, Uekawa, N, Isobe, K	FEBS Lett	2005