Characterization of a promiscuous GTPase-activating protein that has a Bcr-related domain from Caenorhabditis elegans.
Human breakpoint cluster region (bcr) gene product is a member of a group of GTPase-activating proteins that act exclusively on members of the Ras-related Rho subfamily. A complementary DNA was isolated from Caenorhabditis elegans that encoded a polypeptide of 1438 amino acid residues, CeGAP, which contains a domain with sequence similarity to the COOH-terminal segment (GTPase-activating protein region) of Bcr and other known GTPase-activating proteins of the Rho subfamily. It also contains a "pleckstrin homology" motif, present in many signaling proteins including GTPase-activating proteins and nucleotide exchange factors. The Bcr-like domain of CeGAP exhibited activity not only on members of the C. elegans and human Rho subfamily but surprisingly also on C. elegans Ras protein (let-60), human Ras, and Rab3A. CeGAP is therefore the first GTPase-activating protein acting on Ras-related proteins across different subfamilies. Together with the presence of the pleckstrin homology motif, our finding suggests a central and integrative role for CeGAP in a signaling pathway common to Ras and related proteins.
Chen
W
W
Institute of Molecular and Cell Biology, National University of Singapore.
Blanc
J
J
Lim
L
L
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D020690:GTPase-Activating Proteins; D017238:Genes, Helminth; D007438:Introns; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020703:ras GTPase-Activating Proteins
D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D011505:Protein-Tyrosine Kinases; D051562:Proto-Oncogene Proteins c-bcr