Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals

Wendy M. Yee, Paul F. Worley

Research output: Contribution to journalArticle

Abstract

Rheb is a recently described member of the Ras family that was originally identified as an immediate-early gene in brain but is also widely expressed in other tissues. Here we demonstrate that Rheb interacts with and appears to regulate Raf-1 kinase, an essential component of the H-Ras signaling pathway. In direct contrast to H-Ras, however, the interaction of Rheb with Raf-1 is potentiated by growth factors in combination with agents that increase cyclic AMP (cAMP) levels. Protein kinase A-dependent phosphorylation of serine 43 within the regulatory domain of Raf-1 reciprocally potentiates its interaction with Rheb and decreases its interaction with H-Ras. A single amino acid in the G2 effector domain is critical for the differential properties of Rheb. Since Rheb is an immediate- early gene, our studies suggest that Rheb functions in concert with H-Ras to dynamically integrate cAMP and growth factor signaling.

Original languageEnglish (US)
Pages (from-to)921-933
Number of pages13
JournalMolecular and cellular biology
Volume17
Issue number2
DOIs
StatePublished - Feb 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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