生长和分化中的 MAPK/Erk

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. Targets 16 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。