第八章 细胞信号转导(new)PPT.ppt

G-protein-linked receptor desensitization depends on receptor phosphorylation by PKA, PKC, CaMK2 or G-protein-linked receptor kinases(GRKs) G蛋白偶联受体被修饰脱敏 2、磷脂酰肌醇信号通路：双信使通路 效应酶：PLC 第二信使：IP3、DG IP3-Ca2+ pathway and DG-PKC pathway Elevation of cytosolic Ca2+ via the IP signaling pathway Signals?GPLR ?GP ?PLC ?IP3 and DAG (twin signals). IP3 ?IP3 receptor(Ca2+ channel, located at the surface of sER) ? Elevation of cytosolic Ca2+; DAG ?activates PKC ?to phosphoralate Ser and Thr on target proteins. Calcium binds to calcium-binding proteins(CaM) which affects other proteins. IP3信号的终止是通过去磷酸化形成IP2、或磷酸化为IP4 。 DG通过两种途径终止其信使作用： 一是被DG-激酶磷酸化成为磷脂酸，进入磷脂酰肌醇循环； 二是被DG酯酶水解成单酯酰甘油。 Figure?15-32?Two intracellular pathways by which activated C-kinase can activate the transcription of specific genes.????In one (red arrows) C-kinase activates a phosphorylation cascade that leads to the phosphorylation of a pivotal protein kinase called MAP-kinase, which in turn phosphorylates and activates the gene regulatory protein Elk-1. Elk-1 is bound to a short DNA sequence in association with another DNA-binding protein. In the other pathway (green arrows) C-kinase activation leads to the phosphorylation of Ik-B, which releases the gene regulatory protein NF-kB so that it can migrate into the nucleus and activate the transcription of specific genes. 磷脂酰肌醇信号通路 信号分子、G蛋白偶联的受体、G蛋白、 磷脂酶C（PLC）、4，5—二磷酸磷脂酰肌醇（PIP2) 第二信使：IP3和DG。 IP3动员细胞内源Ca，使细胞质中的钙离子浓度增加；DG活化蛋白激酶C（PKC） 3、G蛋白耦联受体介导的离子通道 信号—G蛋白耦联受体—G蛋白 效应蛋白：离子通道 三、离子通道偶联受体介导的信号传递 第四节 酶连受体介导的信号转导 酶偶联的受体 既有信号分子的结合位点，又具有酶的活性或与有酶活性的分子结合，当配体与受体结合后能激活酶的活性。 酶偶联型受体的种类 ①受体酪氨酸激酶 ②受体丝氨酸/苏氨酸激酶 ③受体酪氨酸磷脂酶 ④ 受体鸟苷酸环化酶 ⑤酪氨酸激酶联系的受体 一、受体酪氨酸蛋白激酶及RTK-Ras蛋白信号通路 受体酪氨酸激酶—RTK: 多种生长因子和胰岛素受体 Signaling ligands of RTKs: 1.Nerve growth factor (NGF) 2.Platelet-derived growth factor (PDGF) 3.Fibroblast growth factor (FGF) 4.Epidermal growth factor (EGF) 5.insulin and insulin-like GF(IGF-1) 6. vascular endothelial factor(VEGF) 受体活化：受体二聚化 信号转导的启动 磷酸化的酪氨酸残基（活化的RTK）与具有SH2结构域的分子结合