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First published online October 27, 2005
doi: 10.1242/10.1242/jcs.02671

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CZH proteins: a new family of Rho-GEFs

Nahum Meller^1,, Sylvain Merlot^2,* and Chittibabu Guda³

¹ Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
² Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA
³ Gen^*NY^*sis Center for Excellence in Cancer Genomics and Department of Epidemiology and Biostatistics, State University of New York at Albany, One University Place, Rensselaer, NY 12144, USA

Author for correspondence (e-mail: nm3h{at}virginia.edu)

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.

Key words: Zizimin1, Dock4, Dock3, Zizimin2, Dock2, GTPase

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