信号通路 医学分子生物学PPT.pptVIP

Signaling Transduction in Disease ;“Sickness comes from lost integrity Sickness comes from lack of inner peace The unity of spirit, soul, body and mind Will make You happy and shine” (Taoist poem);stimulus;Principle of CST; 胞外信号分子与膜受体结合，将信号传递至胞浆或核内，调节靶细胞功能的过程。;Basic Mechanism of Transmembrane Signaling;Type 1 Transmembrane Signaling-GC;Type 2 Transmembrane Signaling-EGF;Type 3 Transmembrane Signaling-JAK;Type 4 Transmembrane Signaling-ion channel;Type 5 Transmembrane Signaling--GPCR;G蛋白介导的CST通路;G蛋白介导的CST通路;A G-Protein-Coupled Receptor Or G Protein-linked Receptor 7 transmembrane domains;The disassembly of G-Protein upon stimulation Spontaneous deactivation is very fast, in minutes. However, with the help of RGS (regulator of G protein signaling, a GAP for a unit), signals can be shut off even faster ;;;磷脂酶C(PLC)途径;;;酪氨酸蛋白激酶介导的CST通路;受体酪氨酸激酶的激活及细胞内信号转导复合物的形成;靶基因 转 录;;Interaction between signaling molecules in cytoplasm;Phosphorylation and dephosphorylation--Kinase and phosphatase;2. Acetylation and deacetylation of protein;3. Ubiquitination of protein;4. Ubiquitination-like modification;1. Significance of ubiquitination （1）泛素介导的蛋白质降解 （2）泛素化的非蛋白酶降解功能 2. Significance of ubiquitination-like modification（SUMO） （1）SUMO化调节蛋白质细胞内亚定位 （2）SUMO化调节基因转录活性 （3）SUMO化增加蛋白质的稳定性 （4）SUMO影响DNA的修复 ;细胞信号与疾病;配体异常; 细胞外信号发放异常;炎症细胞活化及炎症介质泛滥的机制示意图 ;导致细胞损伤的理化刺激;受体异常与疾病;;遗传性受体病;;;;遗传性受体病;;遗传性受体病;受体后的信号转导通路成分异常; ;细胞信号与疾病;Wnt/b-catenin signaling and Diseases;Wnt/b-catenin signaling and cancer;结直肠癌 肝细胞癌 生殖系统肿瘤 黑色素瘤 ;Wnt/b-catenin signaling and bone and mineral diseases;Gong et al., Cell 2001;107: 513-523 ;High bone density syndrom LRP5-gain function;TGF-b signaling and Diseases;Role of TGF-? in Cancer 1. Cell-Cycle Regulation and Effects on Proliferation 2. Effects on Metastasis 3. Effects on Angiogenesis 4. Immunosuppressive Effects ;5. TGF-? as a Tumor Suppressor in Transgenic Mice 6. TGF-?? as a Tumor Suppressor in Human Cancer ;Role of TGF-? in Tumor Progression ;The end