Cyclic AMP signalling in Dictyostelium: G-proteins activate separate Ras pathways using specific RasGEFs


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Kae H., Kortholt A., Rehmann H., Insall R., Van Haastert P. J. M. , Spiegelman G. B. , ...More

EMBO REPORTS, vol.8, no.5, pp.477-482, 2007 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 8 Issue: 5
  • Publication Date: 2007
  • Doi Number: 10.1038/sj.embor.7400936
  • Journal Name: EMBO REPORTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.477-482
  • Keywords: Ras, RasGEF, signal transduction, GDP release, Dictyostelium, GUANINE-NUCLEOTIDE EXCHANGE, ADENYLYL-CYCLASE, CELL POLARITY, DISCOIDEUM, IDENTIFICATION, FLUORESCENCE, ROLES
  • Süleyman Demirel University Affiliated: Yes

Abstract

In general, mammalian Ras guanine nucleotide exchange factors (RasGEFs) show little substrate specificity, although they are often thought to regulate specific pathways. Here, we provide in vitro and in vivo evidence that two RasGEFs can each act on specific Ras proteins. During Dictyostelium development, RasC and RasG are activated in response to cyclic AMP, with each regulating different downstream functions: RasG regulates chemotaxis and RasC is responsible for adenylyl cyclase activation. RasC activation was abolished in a gefA(-) mutant, whereas RasG activation was normal in this strain, indicating that RasGEFA activates RasC but not RasG. Conversely, RasC activation was normal in a gefR(-) mutant, whereas RasG activation was greatly reduced, indicating that RasGEFR activates RasG. These results were confirmed by the finding that RasGEFA and RasGEFR specifically released GDP from RasC and RasG, respectively, in vitro. This RasGEF target specificity provides a mechanism for one upstream signal to regulate two downstream processes using independent pathways.