Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals.
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.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Asparagine, Cell Line, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Epidermal Growth Factor, Forskolin, GTP-Binding Proteins, Growth Substances, MAP Kinase Kinase 1, MAP Kinase Kinase Kinase 1, Mice, Mitogen-Activated Protein Kinase Kinases, Molecular Sequence Data, Monomeric GTP-Binding Proteins, Nerve Growth Factors, Neurites, Neuropeptides, Oncogene Protein p21(ras), PC12 Cells, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, Rats, Recombinant Proteins, Serine, Signal Transduction
3T3 Cells, Amino Acid Sequence, Animals, Asparagine, Cell Line, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Epidermal Growth Factor, Forskolin, GTP-Binding Proteins, Growth Substances, MAP Kinase Kinase 1, MAP Kinase Kinase Kinase 1, Mice, Mitogen-Activated Protein Kinase Kinases, Molecular Sequence Data, Monomeric GTP-Binding Proteins, Nerve Growth Factors, Neurites, Neuropeptides, Oncogene Protein p21(ras), PC12 Cells, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, Rats, Recombinant Proteins, Serine, Signal Transduction
Mol. Cell. Biol.
Date: Feb. 01, 1997
PubMed ID: 9001246
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