The gamma-subunit of the coatomer complex binds Cdc42 to mediate transformation.
The Ras-related GTP-binding protein Cdc42 is implicated in a variety of biological activities including the establishment of cell polarity in yeast, the regulation of cell morphology, motility and cell-cycle progression in mammalian cells and the induction of malignant transformation. We identified a Cdc42 mutant (Cdc42F28L) which binds GTP in the absence of a guanine nucleotide exchange factor, but still hydrolyses GTP with a turnover number identical to that for wild-type Cdc42. Expression of this mutant in NIH 3T3 fibroblasts causes cellular transformation, mimicking many of the characteristics of cells transformed by the Dbl oncoprotein, a known guanine nucleotide exchange factor for Cdc42. Here we searched for new Cdc42 targets in an effort to understand how Cdc42 mediates cellular transformation. We identified the gamma-subunit of the coatomer complex (gammaCOP) as a specific binding partner for activated Cdc42. The binding of Cdc42 to gammaCOP is essential for a transforming signal distinct from those elicited by Ras.
Wu
W J
WJ
Department of Molecular Medicine, VMC, Cornell University, Ithaca, New York 14853-6401, USA.
Erickson
J W
JW
Lin
R
R
Cerione
R A
RA
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002471:Cell Transformation, Neoplastic; D020755:Coat Protein Complex I / Q000378:metabolism*; D004789:Enzyme Activation; D006160:Guanosine Triphosphate / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D020755:Coat Protein Complex I; D011993:Recombinant Fusion Proteins; D006160:Guanosine Triphosphate; D020764:cdc42 GTP-Binding Protein