Abstract
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 transformation1,2. 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 (ref. 3). 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 (ref. 4). Here we searched for new Cdc42 targets in an effort to understand how Cdc42 mediates cellular transformation. We identified the γ-subunit of the coatomer complex (γCOP) as a specific binding partner for activated Cdc42. The binding of Cdc42 to γCOP is essential for a transforming signal distinct from those elicited by Ras.
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Acknowledgements
We thank C. Harter and F. Wieland for the anti-α/γCOP antibody and the cDNA for γCOP; A. Musch for advice on VSV-G transport assays; J. Lippinoctt-Schwartz for the plasmid expressing VSV-G; and C. Westmiller for secretarial assistance. We also acknowledge support from the National Institutes of Health.
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Wu, W., Erickson, J., Lin, R. et al. The γ-subunit of the coatomer complex binds Cdc42 to mediate transformation . Nature 405, 800–804 (2000). https://doi.org/10.1038/35015585
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DOI: https://doi.org/10.1038/35015585
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