Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins.
The Rho family GTPases Rac, Rho and Cdc42 are critical in regulating the actin-based cytoskeleton, cell migration, growth, survival and gene expression. These GTPases are activated by guanine nucleotide-exchange factors (GEFs). A biochemical search for Cdc42 activators led to the cloning of zizimin1, a new protein whose overexpression induces Cdc42 activation. Sequence comparison combined with mutational analysis identified a new domain, which we named CZH2, that mediates direct interaction with Cdc42. CZH2-containing proteins constitute a new superfamily that includes the so-called 'CDM' proteins that bind to and activate Rac. Together, the results suggest that CZH2 is a new GEF domain for the Rho family of proteins.
Meller
Nahum
N
Division of Vascular Biology, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla CA 92037, USA.
Irani-Tehrani
Mohammad
M
Kiosses
William B
WB
Del Pozo
Miguel A
MA
Schwartz
Martin A
MA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D004789:Enzyme Activation; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
C466321:DOCK9 protein, human; D020662:Guanine Nucleotide Exchange Factors; D012333:RNA, Messenger; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins