中山大学生命科学院生物化学课件：信号转导2.pptx

Signal-Transduction Pathways信号转导通路 (2)郑利民2007 珠海zhenglm@mail.sysu.edu.cnBiosignaling: How are they regulated?病原侵袭和吞噬对巨噬细胞凋亡的影响及其机制调理后吞噬病原侵袭 RPTKSopEPI-3K死亡信号Rac,CDC42生存信号PKB/Akt细胞凋亡和粘膜屏障损坏细胞存活细胞凋亡是由： 细胞内“死亡/生存”信号之间的精密平衡来决定 干扰该平衡就可改变病原对细胞凋亡的最终影响 The balance between pro- and anti-apoptotic genes/signals determine the cell fate细胞存活细胞凋亡细胞接受到“死亡信号”，不一定就会死亡若同时也接受到“生存信号”，就可继续存活PARTⅠ1 Basic characteristics of signal transduction2 Four general types of signal transducersPARTⅡ1 Regulatory mechanisms2 Some diseases caused by defects in the biosignaling pathwaysRegulatory mechanisms of Bio-signals3.1 Phosphorylation as a regulatory mechanism3.2 Regulation of transcription by steroid hormones3.3 Regulation of the cell cycle by protein kinasesRegulation of Signaling PathwaysSecondmessengersModulatorproteinsTargetproteinsExternalsignalsFunctionHormones cAMPOdorants cGMPDrugs Ca2+Light DAG IP3Mitogenichormones TyrosineGrowth kinasesfactorsPlasma membranestructuralproteinsAnd enzymesproteinkinaseAnd phosphatasemetabolicorphysiologicalresponsesProtein Kinases 1: GPCRs (5%), 2: Kinases (2.8% genome) ~ 25% of the mammalian intracellular proteins undergoes reversible phosphorylationProtein kinases (534 human kinases)Ser/thr Kinases comprise 80% of all protein kinasesAGC 蛋白激酶 n NTPn NDP 蛋白质 蛋白质-n Pi n Pi蛋白磷酸酶 H2OPhosphorylation de-phosphorylation are the most common regulatory mechanisms, mediated by protein kinase and phosphatase, respectively Nobel Prize in Physiology and Medicine 1992“Reversible protein phosphorylation as a biological regulatory mechanismEdmond H. Fischer Eldwin G. KrebsJ. Biol. Chem. 216:121-132, 1955USA Activation of G Protein–Coupled ReceptorscAMPPhosporylatingcellular proteinsPKAResponseActivation of Ras proteinGEF：Guanine nucleotide Exchange FactorGAP：GTPase Activating Protein FFFFPiPiGEFGEFGAPGAPRasRas--GTPGTPRasRas--GDPGDPGrb2Grb2SHCSHCRas蛋白的上游和下游信号通路 PI3K的活化机制及PIP3磷酸酶(PI3K is a downstream target of Ras)PI3K