信号转导学院 - 赢在信号通路

通路描述：

MAPK/Erk 信号级联放大通过生长和分化中涉及的各种不同受体进行激活，包括受体酪氨酸激酶 (RTKs)、整合素以及离子通道。由不同的刺激物激活的级联反应的特定组分差异较大，但通路的结构通常包含一组对接蛋白（Shc、GRB2、Crk 等），它们将受体连接到一个鸟苷酸交换因子上（SOS、C3G 等），信号则转导至小分子 GTP 结合蛋白 (Ras，Rap1)，后者再激活级联中的核心单位，包括一个 MAPKKK (Raf)、一个 MAPKK (MEK1/2) 和 MAPK (Erk)。激活的 Erk 二聚物可在胞质中调控靶蛋白，也可转运入胞核，在核内磷酸化多种调控基因表达的转录因子。

主要文献：

    Anjum R, Blenis J (2008) The RSK family of kinases: emerging roles in cellular signalling. Nat. Rev. Mol. Cell Biol. 9(10), 747–58.
    Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta 1802(4), 396–405.
    Keyse SM (2008) Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 27(2), 253–61.
    De Luca A, Maiello MR, D'Alessio A, Pergameno M, Normanno N (2012) The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets16 Suppl 2, S17–27.
    Mendoza MC, Er EE, Blenis J (2011) The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem. Sci.36(6), 320–8.
    Romeo Y, Zhang X, Roux PP (2012) Regulation and function of the RSK family of protein kinases. Biochem. J.441(2), 553–69.
    Roskoski R (2012) MEK1/2 dual-specificity protein kinases: structure and regulation. Biochem. Biophys. Res. Commun. 417(1), 5–10.
    Tidyman WE, Rauen KA (2009) The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr. Opin. Genet. Dev.19(3), 230–6.

感谢来自美国马萨诸塞州波士顿哈佛医学院的 John Blenis 教授审阅了此图。