xiaoG蛋白与信号转导.pptVIP

小G蛋白 Ras蛋白(Rat sarcoma) Harrey和Kirfen鼠肉瘤病毒上发现，称H-ras、K-ras，人神经母细胞瘤上发现N-ras。 与G蛋白相同：GTP/GDP转换；GTPase 不同：受酪氨酸蛋白激酶调节，需蛋白中介：接头蛋白(GRB2)和Sos、GTP酶激活蛋白(GAPs)，类似G蛋白中的α亚基。 蛋白质相互作用的调控结合元件(modular binding domain) 概念：是蛋白质分子中的特殊结构域，是信号分子相互识别的部位。 种类： SH2 结构域(src homology 2 domain)：介导信号分子与含磷酸酪氨酸蛋白质分子的结合 SH3 结构域(src homology 3 domain)：介导信号分子与富含脯氨酸蛋白质分子的结合 PH 结构域(pleckstrin homology domain) PTB结构域(protein tyrosine binding domein)，识别含磷酸酪氨酸的基序 主要细胞信号转导途径 细胞内受体介导 信号转导 离子通道型受体及其信号转导 G蛋白偶联受体及其信号转导 单次跨膜受体介导的信号转导 细胞信号转导的基本路线 细胞内受体介导的信号转导过程 (Signaling Mediated by Intracellular Receptors) 受体属转录因子 没有激素时：受体—热休克蛋白(heat shock proteins,Hsps)复合物，阻止受体向细胞核移动及与DNA的结合。 激素与受体结合后：Hsps解离，激素—受体复合物，结合于DNA上的激素反应元件(hormone response element,HRE) * Activation of Ras following binding of a hormone (e.g., EFG) to a receptor tyrosine kinase (RTK) Sos: Son of sevenless GRB2: Growth factor receptor-bound protein Binding of SH2-containing intracellular signaling proteins to an activated PDGF receptor PDGF: platelet-derived growth factor SH2 domain SH2 domain bound to short target peptide SH2 domain (globular structure) and a segment of a receptor (stick model) fit together in part because a positive charged pocket in SH2 is attracted to a negatively charged phosphate. Also, the nearby amino acids in the receptor fit snugly into a hydrophobic groove on SH2. The three-dimensional structures of SH2 domains in different proteins are very similar. Each binds to a distinct sequence of amino acid surrounding a phosphotyrosine residue. 5-6 anti-parallel ?-strands Generally bind to Pro-rich peptides with the minimal consensus Pro-X-X-Pro. SH3 domain Cell Signaling 一、General Principles of Cell Signaling 二、Signaling Mediated by Intracellular Receptors Steroid hormones, thyroid hormones, retinoids, vitamin D HRE: hormone response element Bound hormone- receptor complex can either enhance or suppress the expression of specific genes adjacent to HREs. The ability of