Yee W M, Worley P F
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Cell Biol. 1997 Feb;17(2):921-33. doi: 10.1128/MCB.17.2.921.
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.
Rheb是Ras家族中最近被描述的成员，最初被鉴定为脑中的即早基因，但在其他组织中也广泛表达。我们在此证明，Rheb与H-Ras信号通路的重要组成部分Raf-1激酶相互作用并似乎对其进行调节。然而，与H-Ras形成直接对比的是，Rheb与Raf-1的相互作用在生长因子与增加环磷酸腺苷（cAMP）水平的试剂联合作用下得到增强。Raf-1调节域内丝氨酸43的蛋白激酶A依赖性磷酸化反过来增强其与Rheb的相互作用，并降低其与H-Ras的相互作用。G2效应域中的单个氨基酸对Rheb的不同特性至关重要。由于Rheb是一个即早基因，我们的研究表明，Rheb与H-Ras协同作用，动态整合cAMP和生长因子信号。
