_細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)ppt課件

1、Year Recipient Prize Area of Research 2000 A. Carlsson, P. Greengard, E. Kandel M & P Signal transduction in the nervous system 1999 G. Blobel M & P Signal hypothesis of protein translocation 1998 R. Furchgott, L. Ignarro, F. Murad M & P Role of NO as cellular messenger 1994 A. Gilman, M

2、. Rodbell M & P Structure and function of GTP-binding(G) proteins 1992 E. Fischer, E. Krebs M & P Alteration of enzyme activity by phosphorylation/dephosphorylation 1971 E.W. Sutherland M & P Mechanism of hormone action and cyclic AMP 2019 L. H. Hartwell, R. T. Hunt, P. M. Nurse M&P

3、key regulators of the cell cycle2019 S. Brenner, H. R. Horvitz, J. E. Sulston M&P ApoptosisNobel prizes awarded for research Nobel prizes awarded for research in signal transductionin signal transductionApathyMarvelousUncontrollablesignalcellchange增殖增殖分化分化代謝代謝功能功能應(yīng)激應(yīng)激凋亡凋亡 or or lostdisease GTPGD

4、P效應(yīng)蛋白通道載體PLC核受體EDNA DNAUp streamDown End effectorG G蛋白蛋白鳥(niǎo)苷酸環(huán)化酶GC酪氨酸蛋白激酶核受體核受體2100028000位于細(xì)胞內(nèi)只需G 功能Ras ,微管蛋白 亞基 在將信號(hào)從細(xì)胞膜外傳送至細(xì)胞核的過(guò)程中，在將信號(hào)從細(xì)胞膜外傳送至細(xì)胞核的過(guò)程中，RasRas蛋白起著非常重要的作用。整個(gè)過(guò)程開(kāi)蛋白起著非常重要的作用。整個(gè)過(guò)程開(kāi)始于生長(zhǎng)因子如始于生長(zhǎng)因子如EGFEGF或或PDFGPDFG等與各自等與各自受體的細(xì)胞外功能域結(jié)合受體的細(xì)胞外功能域結(jié)合IP3、Ca2+-鈣調(diào)蛋白激酶鈣調(diào)蛋白激酶腺苷酸環(huán)化酶腺苷酸環(huán)化酶ACDG-蛋白激酶蛋白激酶CPL

5、C -+Ras-MAPKPLC-PIP2PI3K增殖分化GFTPK靶蛋白靶蛋白磷酸化磷酸化Grb2SosRafMEKERK靶蛋白靶蛋白磷酸化磷酸化轉(zhuǎn)錄因子轉(zhuǎn)錄因子磷酸化磷酸化靶基因靶基因轉(zhuǎn)錄轉(zhuǎn)錄PLCPIP2DAGPKCIP3Ca2+50 kindsRasJAKJAK-STAT通路JAKJAKSTATCa2+精精aaNOGTPcGMPRcytokinesPKG血管舒張血管舒張Ach-RGCGCNONO合酶合酶Vascular endothelial cellVascular smooth musclecell血管血管GCGC信號(hào)轉(zhuǎn)導(dǎo)系統(tǒng)信號(hào)轉(zhuǎn)導(dǎo)系統(tǒng)?COCa2+argNOGTPcGMPRcyt

6、okinescytokinesPKGVascular dilationGCsGCNONO synthaseVascular GC signal transduction systemVascular GC signal transduction system?VECVSMCAch-RCOHHSPHHHHHRE核轉(zhuǎn)錄因子mRNAproteinRRRRHSPHSPcell membrane類固醇激素受體家族甲狀腺激素受體家族糖鹽性糖鹽性激素受體，激素受體，胞漿胞漿受體受體與與HSP結(jié)結(jié)合合T3VitD維維甲酸，不與甲酸，不與HSP結(jié)合，同源結(jié)合，同源或異源二聚或異源二聚體與體與DNA或或其它蛋白其

7、它蛋白質(zhì)結(jié)合質(zhì)結(jié)合signalRDNAmRNAprotein?pathwayG蛋白蛋白GCTPK核受體核受體受體病受體下調(diào)或減敏受體上調(diào)或增敏一、受體異常與疾病遺傳性受體病遺傳性受體病本身免疫受體病本身免疫受體病繼發(fā)性受體異常繼發(fā)性受體異常家族性高膽固醇血癥家族性高膽固醇血癥*家族性腎性尿崩癥家族性腎性尿崩癥甲狀腺素抵抗綜合征甲狀腺素抵抗綜合征*重癥肌無(wú)力重癥肌無(wú)力本身免疫性甲狀腺病本身免疫性甲狀腺病 損傷性：膜磷脂分解代償性：ligandLDL-R1、合成妨礙、合成妨礙2、轉(zhuǎn)運(yùn)妨礙、轉(zhuǎn)運(yùn)妨礙3、與配體結(jié)合妨礙、與配體結(jié)合妨礙4、內(nèi)吞缺陷、內(nèi)吞缺陷數(shù)目GTPGDP效應(yīng)蛋白通道載體PLCGTPGDPGs+GTPACCl-、H2OAdult?child+DNANF- BRTNFa酸性神經(jīng)鞘磷脂酶神經(jīng)鞘磷脂神經(jīng)酰胺蛋白激酶+NF-kBIkB IkBNF-kB基因轉(zhuǎn)錄細(xì)胞因子,炎癥介質(zhì)CD14TLRLPS-LBPMyd88TRAF6IRAKNIKIKKIkBP65 P50NF-kBP65 P50mRNACytokine adhesion mol chemotactic F NO thynthase?IL-1RTNF-R1IL-1bTNFa遺傳性數(shù)量 親和力 TPK活性 甘a.a1008突變?yōu)轭Ra.a本身免疫性繼發(fā)性高胰島素血癥 繼發(fā)性下調(diào) 絲/蘇aa激酶活性VSMC編碼非受