Rich, a rho GTPase-activating protein domain-containing protein involved in signaling by Cdc42 and Rac1.
A previously unidentified Rho GTPase-activating protein (GAP) domain-containing protein was found in a yeast two-hybrid screen for cDNAs encoding proteins binding to the Src homology 3 domain of Cdc42-interacting protein 4 (CIP4). The protein was named RICH-1 (RhoGAP interacting with CIP4 homologues), and, in addition to the RhoGAP domain, it contained an N-terminal domain with endophilin homology and a C-terminal proline-rich domain. Transient transfections of RICH-1 indicated that it bound to CIP4 in vivo, as shown by co-immunoprecipitation experiments, as well as co-localization assays. In vitro assays demonstrated that the RhoGAP domain of RICH-1 catalyzed GTP hydrolysis on Cdc42 and Rac1, but not on RhoA. Ectopic expression of the RhoGAP domain as well as the full-length protein interfered with platelet-derived growth factor BB-induced membrane ruffling, but not with serum-induced stress fiber formation, further emphasizing the notion that, in vivo, RICH-1 is a GAP for Cdc42 and Rac1.
Richnau
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Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S-751 24 Uppsala, Sweden.
Aspenström
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D020690:GTPase-Activating Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D020690:GTPase-Activating Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C485787:Trip10 protein, mouse; C085379:rho GTPase-activating protein; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein