title: Characterization of the C. elegans gap-2 gene encoding a novel Ras-GTPase activating protein and its possible role in larval development.
abstract: BACKGROUND
  The Ras signalling pathway plays several important roles in the development of the nematode Caenorhabditis elegans. So far, two types of Ras-GTPase activating proteins (Ras-GAPs) have been identified in this organism. To aid the study of the regulation and function of the Ras pathway, we set out to isolate a new GAP gene from C. elegans by transcomplementation of the fission yeast gap1 mutant.
  
  
  RESULTS
  We isolated a C. elegans cDNA that encoded a protein which was similar to, but not exactly homologous with mammalian p120 Ras-GAP. This gene, named gap-2, generated at least nine distinct mRNA species through transcription from different promoters and subsequent alternative splicing involving 25 exons. These isoforms were differentially expressed among tissues. A deletion of gap-2 caused no obvious phenotype by itself, but a loss of gap-2 function could suppress larval lethality in both let-23 and let-60 reduction-of-function mutants, in which the Ras activity was lowered.
  
  
  CONCLUSIONS
  C. elegans gap-2 encodes a novel Ras-GAP, which is similar to vertebrate p120 but which may constitute a new GAP subfamily. gap-2 mRNA isoforms arise by an unusually extensive variation in initiation sites and associated alternative splicing, and each isoform may play a distinct role in specific tissues. GAP-2 appears to function as a negative regulator of LET-60 Ras during larval development.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hayashizaki
authors.forename: Y
authors.initials: Y
authors.lastname: Iino
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D020690:GTPase-Activating Proteins; D017238:Genes, Helminth; D005816:Genetic Complementation Test; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012568:Schizosaccharomyces / Q000235:genetics; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins