Rheb Inhibits C-Raf Activity and B-Raf/C-Raf Heterodimerization
作者： Magdalena Karbowniczek , Gavin P. Robertson , Elizabeth Petri Henske
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摘要: The Ras-Raf-MEK signaling cascade is critical for normal development and activated in many forms of cancer. We have recently shown that B-Raf kinase interacts with inhibited by Rheb, the target GTPase-activating domain tuberous sclerosis complex 2 gene product tuberin. Here, we demonstrate first time activation Rheb associated decreased C-Raf phosphorylation at residues Ser-446 Ser-338, respectively, concomitant a decrease activities both kinases heterodimerization C-Raf. Importantly, impact on B-Raf/C-Raf activity are rapamycin-insensitive, indicating they independent mammalian rapamycin-Raptor complex. In addition, found inhibits association H-Ras. Taken together, these results support central role regulation Ras/B-Raf/C-Raf/MEK network.
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