病理生理学信号转导.ppt

; ;? ;;signal;;G蛋白介导的细胞信号转导途径;（1）cAMP—第一个被发现的第二信使; 1896 ~ 1984 (in Prague, then Austria);;;;;;（2）PKA----Pro P*/P-;;?? β-R α2-R，M-R α1-R，ET-R Gsα Gi Gqα AC PLCβ cAMP PIP2 IP3 PKA DAG(DG) gene PKC;1992----Pro P*/P-;;（3）GPCR/GP——受体/胞浆中的GTP酶;G蛋白介导的细胞信号转导途径;Alfred G. Gilman University of Texas Southwestern Medical Center at Dallas Dallas, TX, USA ;A mutated lymphoma cell was found to contain a normal receptor and a normal cyclic AMP-generating enzyme but was yet unable to respond because it lacked the transducer. This was a good system to assay purified G proteins  ;G蛋白——与鸟嘌呤核苷酸可逆性结合的蛋白质家族;;;;Signal transduction cascades that activate small G-proteins have now been found in a wide range of cells ;PLCβ;?;?;;PLCβ;;;anti-PIP2 antibody;蛋白激酶C的作用;蛋白激酶C参与基因表达调控;????????????????????????????????????????????????????????????????????????????????????;　在肝细胞中，蛋白激酶C与蛋白激酶A协作磷酸化糖原合成酶，抑制葡萄糖聚合酶（glucose-polymerizing enzyme）的活性，促进糖原分解、抑制糖原合成; 由蛋白激酶C介导的某些反应;某些激活磷脂酶C的信号分子;Sutherland 1971;Otto Loewi ;;2.Tyrosine protein kinase pathway;Pro P*/P-——整合调控;1992----Pro P*/P-;Receptor Tyrosine Kinases; 轴突再生新希望-----EGFR抑制剂 神经损伤后，髓鞘及其邻近的神经胶质可释放抑制轴突再生的分子，但机制不清。 　　 美国波士顿儿童医院研究：在神经损伤后，表皮生长因子受体（EGFR）的激活似乎阻碍其轴突再生过程。 如果EGFR的酪氨酸激酶活性被抑制，那么上述分子就不再抑制轴突再生。局部注射EGFR抑制剂可促进小鼠损伤视神经纤维再生。 ;(1)Receptor tyrosine protein kinase, RTK (20 types);;;;MAPK fig; 蛋白激酶的种类（5类）;;PKB/Akt结构模式图;;;(2)PTK-linking receptor;Roles of Cytokines in Hematopoiesis;JAK-STAT Activation by Interferon Receptor;FERM domain: similar to those found in the cytoskeletal adaptor proteins band Four point one, Ezrin, Radixin and Moesin ;;3.GC pathway;1998------NO, EDRF？;Robert F. Furchgott ;Hemoglobin (yellow) exposed to endothelial cells t