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CZH proteins: a new family of Rho-GEFs

2005; The Company of Biologists; Volume: 118; Issue: 21 Linguagem: Inglês

10.1242/jcs.02671

1477-9137

Nahum Meller, Sylvain Merlot, Chittibabu Guda,

Cellular transport and secretion

The Rho family of small GTPases are important regulators of multiple cellular activities and, most notably, reorganization of the actin cytoskeleton. Dbl-homology (DH)-domain-containing proteins are the classical guanine nucleotide exchange factors (GEFs) responsible for activation of Rho GTPases. However, members of a newly discovered family can also act as Rho-GEFs. These CZH proteins include: CDM (Ced-5, Dock180 and Myoblast city) proteins, which activate Rac; and zizimin proteins, which activate Cdc42. The family contains 11 mammalian proteins and has members in many other eukaryotes. The GEF activity is carried out by a novel, DH-unrelated domain named the DOCKER, CZH2 or DHR2 domain. CZH proteins have been implicated in cell migration, phagocytosis of apoptotic cells, T-cell activation and neurite outgrowth, and probably arose relatively early in eukaryotic evolution.