基础肿瘤理论与实践 肿瘤学2015-12 信号传导与疾病 ZHAO.pptVIP

信号传导与疾病（Signal transduction and disease）;The Hallmarks of Cancer;Cell-to-cell communication by extracellular signaling usually involves six steps;;;“wiring” of cell regulatory circuits;Intercellular Signaling:how cells communicate with one another;Examples of Signaling;Extracellular Signals Bind to Different Types of Receptors; 1951年，第一个生长因子神经生长因子 NGF发现 Rita Levi-Montalcini Stanley Cohen 1955年，Receptor 的概念正式提出 1957年，第二信使cAMP发现 Earl Sutherland 50 年代中期，磷酸化的发现和第一个蛋白激酶的分离 Edwin Krebs Fischer 70年代，G蛋白和G蛋白连接受体的发现和克隆 Alfred G. Gilman Martin Rodbell 发现癌基因v-src 的蛋白产物是蛋白酪氨酸激酶 Michael Bishop Harold E. Varmus ;;;;;;; ;刺激细胞增殖的因子 生长因子（growth factor） 是一类以刺激细胞生长为特征的多肽 受体具有酪氨酸激酶活性 特异性 多样性 家族性 交叉性 细胞因子（cytokine） 白介素、 血细胞刺激因子、干扰素 受体本身不具有激酶活性 激素和神经递质 ;其他重要的细胞外因子 抗原 肿瘤坏死因子（tumor necrosis factor, TNF） 粘附分子(adhesion molecules) 纤粘连蛋白（Fibronectine, Fn ）层粘连蛋白（laminin, Lm） 胶原蛋白（collagen, coll）;受体;酪氨酸激酶受体Tyrosine-kinase Receptors;Class;G蛋白连接受体 G-protein Coupled Receptors;G protein-coupled receptors;olfactory R, adenosine R, cannabinoid R, ......;G Protein;ai3;;;Each cytokine/hematopoietic receptor is a composite of structurally distinct protein domains. Members of this receptor family contain one, two, or even three polypeptides. The transmembrane domain consists of a single alpha helix of about 20 amino acids. Ligand binding occurs at a domain near the transmembrane domain ;Ligand binding occurs in a region near the transmembrane domain. The cytosolic domain of a cytokine receptor does not possess intrinsic catalytic activity. Rather, the ligand-bound receptor recruits and activates the cytosolic tyrosine kinase JAK. JAK substrates include JAK itself, the receptor, IRS molecules, and the transcriptional activator STAT. Phosphorylated JAK also interacts with other signal transduction proteins through SH2 domains ;粘附因子受体 Adhesion Molecules Receptors;连接蛋白;;Other proteins have homologies to