课件：蛋白激酶与磷酸酶.pptx

蛋白激酶与磷酸酶;蛋白质翻译后修饰;磷酸化修饰的氨基酸;蛋白质的磷酸化修饰;蛋白激酶将ATP末端的磷酸基团转移到蛋白质侧链的羟基上； 磷酸酶催化蛋白质侧链上磷酸基团的水解。; ~30%的蛋白质可以发生磷酸化修饰;蛋白激酶的结构;蛋白激酶的分类;受体酪氨酸激酶（RTK）;Six subfamilies of receptor tyrosine kinases involved in cell growth and differentiation. Only one or two members of each subfamily are indicated. Note that the tyrosine kinase domain is interrupted by a kinase insert region in some of the subfamilies. The functional significance of the cysteine-rich and immunoglobulin-like domains is unknown. ;受体二聚体化与激酶的激活;Binding of insulin to the alpha subunits causes the beta subunits to phosphorylate themselves (autophosphorylation), thus activating the catalytic activity of the receptor. ;MAPKK可同时催化MAPK激酶的T与Y的磷酸化修饰： 磷酸化位点的三肽模体 — TXY ERK — TEY p38 — TGY JNK — TPY MAPK是通过Thr和Tyr的双位点同时磷酸化而被激活。;磷酸肌醇循环;磷酸肌醇循环;;Western blot analysis of whole cell lysates of Jurkat cells, with 0.1?M calyculin A for 20 minutes prior to lysis, using Phospho-Thr antibody. ; 丝氨酸/苏氨酸蛋白磷酸酶 (PP1, PP2A)； 酪氨酸蛋白磷酸酶 (PTP1B)； 双特异性蛋白磷酸酶 (DUSP1)； 脂质磷酸酶 (PTEN, SHIP)。;Ser/Thr与Tyr蛋白磷酸酶;;PP2A磷酸酶的多样性与复杂性;翻译后修饰对磷酸酶功能的调控作用;?磷酸化修饰的级联反应;?MAPK信号级联反应;?磷酸酶的信号级联反应;During interphase, Cdc25 is held inactive via by inhibitory phosphorylation at Ser287 and 14-3-3 binding. Likewise, PP2A/B56δ maintains Thr138 in the dephosphorylated state. At the G2/M transition, Cdc25 is activated in a stepwise fashion. First, Cdk2 phosphorylates Thr138 which triggers the release of 14-3-3. Phosphorylated keratin intermediate filaments assist in 14-3-3 removal from Cdc25 and Plx1 may also play a role in this process. Exposed Ser287 is then readily dephosphorylated by PP1, inducing the activation and nuclear translocation of Cdc25 and dephosphorylation of Cdc2. Once activated, Cdc2/Cyclin B phosphorylates multiple sites on Cdc25, enhancing its activity and preventing inactivation. Cdc2/Cyclin B may also activate the MAP kinase cascade which can phosphorylate Cdc25 in a parallel positive feedback loop. ;位点特异性的磷酸化修饰;蛋白质的磷酸化修饰分析;生物质谱