海南4+1

RTK-Ras-MAPK信号转导通路
来源/作者:中国标准物质网  日期:2015-09-09

XIAOFENZILIANGGDANBAIJIAZUCHENGYUANZHI-Ras,SHIRTKJIEDAODEXINHAOTONGLUZHONGDEYIZHONGGUANJIANZUFEN,CANYUXIBAOSHENGZHANGDIAOKONGHEZENGZHI,HAIYINGXIANGXIBAOFENHUA、XINGTAIFASHENGHEDIAOWANG。HUOHUADESHOUTILAOANSUANJIMEIDEXINHAOKUAMOCHUANDIDAORasDANBAI,TONGGUODANBAIJIMEIDEJILIANFANYINGCHUANSONGDAOXIBAOHE。ZHEITIAOTONGLUYOUCUXIBAOFENLIEXINHAORUSHENGZHANGJISULEIJIHUO,SUOYIBEICHENGWEISILIEYUANHUOHUADANBAIJIMEITONGLU(mitogenic activated proteinkinase pathway, MAPKTONGLU)。

SHOUTIXINGRTK-Ras-MAPKXINHAOZHUANDAOTUJING,SHIXIBAOWAIXINHAOCHUANDIDAOXIBAOHENEIDEZHONGYAOTONGDAO,ZUCHENGHEZHUANDAOGUOCHENGKEJIANDANZONGJIEWEI:PEITI(LIRUSHENGZHANGYINZI)→SHOUTIXINGLAOANSUANDANBAIJIMEIRTK→HANYOUSH2/SH3JIEGOUDEJIETOUDANBAI(LIRUGrb2 )→NIAOGANSUANSHIFANGYINZI(LIRUSOS)→RasDANBAI→MAPKLIAN→SHENGWUXUEXIAOYING。

SHOUTIXINGLAOANSUANDANBAIJIMEIDEHUOHUA

SHOUTIXINGRTKDADUOSHUYUXIBAOSHENGZHANGYINZISHOUTIJIMOUXIEAIJIYINBIANMADECHANWU,LIRUYIDAOSUSHOUTI、BIAOPISHENGZHANGYINZISHOUTI、XUEXIAOBANYANSHENGSHENGZHANGYINZISHOUTIDENG。DANGPEITIYUSHOUTIBAOWAIQUJIEHEHOU,YINQIXIANGLINDESHOUTIFASHENGERJUHUA,JINERSHOUTIBAONEIQUDETKBEIJIHUO,BICIJIANGDUIFANGDEMOUXIELAOANSUANCANJILINSUANHUA,DAOZHISHOUTIHUOHUA。

HUOHUADESHOUTISHIBIEHANSH2JIEGOUYUDEJIETOUDANBAI

ZAISHOUTIXINGRTK-Ras-MAPKXINHAOZHUANDAOTUJINGZHONG,JIETOUDANBAIGrb2TONGGUOQISH2JIEGOUYUSHIBIEBINGJIEHEDAOHUOHUARTKDELINSUANHUALAOANSUANCANJISHANG,ZAIRTKYUXIAYOUXINHAODANBAIZHIJIANJIAQIYIZUOQIAOLIANG。Grb2CHUHANYOUYIGESH2JIEGOUYUWAI,TONGSHIHAIJUYOULIANGGESH3JIEGOUYU。SH3FUHANFUANSUAN,YOUYUE60GEANJISUANCANJIGOUCHENG,TADEGONGNENGSHISHIBIEBINGJIEHEXIAYOUDELINGYIGEXINHAODANBAIFENZI——NIAOGANSUANJIAOHUANYINZI,JISOS (son of sevenless ),SHIBIEBUWEISHISOSZHONGFUHANFUANSUANDEQUDUAN。Grb2TONGGUOYUSOSJINMIJIEHE,JINGHEXISUANJIAOHUAN,JIANGXINHAOCHUANDIDAORas。ZAIGrb2-SOSFUHETIZHONG,Grb2DEZUOYONGSHIOULIANSHOUTILAOANSUANJIMEIHERasDANBAI。

ZAISOSDEZUOYONGXIAJIHUORasDANBAI

(1)NIAOGANSUANJIAOHUANYINZISOS ZAIHUOHUADERTKYURasDANBAIZHIJIANFASHENGDEXINHAOCHUANDIYOUNIAOGANSUANJIAOHUANYINZISOSJIEDAO,SOSHEJIETOUDANBAIGrb2JIEHEXINGCHENGDEFUHEWUGOUCHENGLEJIHUOSHOUTIYURasDANBAIZHIJIANDELIANJIEJIEGOU。ZAIXIBAOJINGXIZHUANGTAISHI,Grb2TONGGUOLIANGGESH3JIEGOUYUYUSOSJIEHECHENGFUHEWU,CUNZAIYUBAOJIANGZHONG。DANGRTKSHOUTIBEIJIHUOSHI,TONGGUOGrb2 NDUANDESH2JIEGOUYUJIANGGrb2-SOSFUHEWUYUSHOUTIXIANGLIAN,BINGJIANGQIYIZHIXIBAOMOSHANGMUJISOS,TIGAOSOSZAIZHIMOSHANGDEJUBUNONGDU。SOSJUYOUHEXISUANZHUANYIMEIDEHUOXING,ZAITADEZUOYONGXIAJIHUOXIAYOUBADANBAIRasDANBAI。Grb2-SOSFUHEWUCONGBAOJIANGZHONGDINGWEIDAOBAOMOKENENGSHIJIHUODESHOUTIYURasDANBAIJIEHEDEXIANSUBUZHOU,DANGLIANGZHONGDANBAIDOUDAODAXIBAOMOSHIJIHUOXINHAOCHUANDI,RasDANBAICHUYU“KAI”DEZHUANGTAI。

(2) RasDANBAI RasDANBAIYOUYITIAODUOTAILIANGOUCHENG.SHIYIGEFENZIZHILIANGWEI21kDDEDANTIGTPMEI。YOUYUANAIJIYINrasBIANMAERDEMING,TASHIRTKXINHAOZHUANDAOTONGLUZHONGDEZHUYAOCHENGYUAN。RasDANBAISHIMOJIEHEXINGDANBAI,XINGZHILEISIYUGDANBAIDEGaYAJI,DANQIFENZILIANGXIAO,YOUYUE170GEANJISUANCANJIGOUCHENG,GUYOUCHENGWEIXIAOGDANBAI。RasDANBAISHANGJUYOUYUGTPHUOGDPJIEHEDEBUWEI,DANGQIYUGDPJIEHESHIWEISHIHUOXING,YUGTPJIEHESHIWEIJIHUOXING。DANGSOSBEIMUJIDAOXIBAOMO,BINGYUDIWURasDANBAIKAOJINSHI,ZAISOSHEGANSUANZHUANYIMEIDEZUOYONGXIA,GDPTUOLUOTONGSHIJIEHE GTP, RasDANBAIJIBEIHUOHUA。

ZHIYOUGTPJIEHEXINGDERasNENGGOUJIXIAYOUCHUANDIXINHAO,SUOYIGTPJIEHEXINGDECHIXUSHIJIANFEICHANGZHONGYAO,ZHEISHIYOUGTPDESHUIJIESULVJUEDINGDE。DANJIURasDANBAILAIJIANG,QIGTPSHUIJIEDEGUYOUSULVHENDI,YUGDPXINGCHENGDEFUHETIJIELIYESHIFENHUANMAN。DANZAIXINHAOCHUANDIDEGUOCHENGZHONG,RasTEYIXINGDENIAOXISUANJIAOHUANDANBAI(G-nucleotide exchange proteins, GEF)HEGTPMEIJIHUODANBAI(GTPaseactivatingprotein, GAP)JIASUZHEILIANGGEGUOCHENG,CHENGWEIRasDANBAIZHUANHUANKAIGUANDEGUANJIANCHENGFEN。

QIDONGMAPKJILIANFANYING

ZAISHOUTIXINGRTK-Ras-MAPKXINHAOZHUANDAOTUJINGZHONG,JIHUODERasDANBAIDEXIAYOUXINHAODANBAISHISIANSUAN/SUANSUANTEYIXINGDANBAIJIMEIRaf。 RafJIMEISHIMAPKXINHAOXITONGDEZUCHENGBUFEN,TADEHUOHUAKEYINFADANBAIZHILINSUANHUAJILIANFANYING。MAPKXITONGBAOKUOMAPK(SILIEYUANJIHUODANBAIJIMEI)、MAPKK (MAPKJIMEI)、MAPKKK (MAPKKJIMEI)。ZHEISHIYIZUMEIJIANDIWUDEDANBAIZHIFENZI,BUTONGDANBAIJIMEIZAIMAPKJILIANXITONGZHONGDEWEIZHIQUJUEYUQIDIWUTEYIXING。

(1) MAPKKK (Raf) MAPKKKJUYOUSIANSUAN/SUANSUANDANBAIJIMEIHUOXING,TAKEJIANGMAPKKLINSUANHUAERJIHUO,SHIJINRUMAPKXINHAOZHUANDAODEQISHIDIAN。RafDANBAISHIDAIBIAOXINGDEMEI,YOUGTPJIEHEXINGRasDANBAIJIHUOHOU,SHIXIAYOUMAP-KKDANBAIDELIANGGESIANSUANCANJILINSUANHUA。RafSHIMAPKJILIANFANYINGDEDIYIGEFENZI,YOUCIQIDONGMAPKDESANJIJILIANFANYING。RasDANBAIBENSHENWUDANBAIJIMEIHUOXING,RUHESHIMAPKKKFASHENGLINSUANHUAZHEIYIDIANSHANGWEIHUODEMINGQUEZHENGSHI,KENENGHEDANBAIJIMEIC (PKC)DECANYUYOUGUAN。

(2) MAPKK (MEK) MAPKKSHIYIZHONGSUANSUAN/LAODANSUANDANBAIJIMEI,SHUYILEITESHUDEDANBAIJIMEI,DUIDANBAIDIWULINSUANHUAWEIDIANSHANGDEANJISUANCANJIJUYOUSHUANGZHONGTEXING,TAKEYISHIWEIYUQIXIAYOUMAPKDESUANSUANHELAOANSUANCANJILINSUANHUAERJIHUO。ZHEIXIELINSUANHUADEWEIDIANBEICHENGWEIMAPKDE“TEY”TEZHENGSHUNXU。ZAISHOUTIXINGRTK-Ras-MAPKXINHAOZHUANDAOTUJINGZHONG,SHUYUMAPKKDEDANBAISHIMEK.。RafZUOYONGYUMEK,SHIZHILINSUANHUAERHUOHUA。HUOHUADEMEKZAIZUOYONGYUSHUYUMAPKJIAZUDEERK,SHIQILINSUANHUAERHUOHUA。

(3) MAPK (ERK) MAPKSHIYIZHONGJUYOUSHUANGZHONGCUIHUAHUOXINGDEDANBAIJIMEI,JIKECUIHUASIANSUAN/SUANSUANCANJILINSUANHUA,YOUNENGCUIHUALAOANSUANCANJILINSUANHUA。YINCITAJUYOUGUANGFANDECUIHUAHUOXING,JIEDAOXUDUOZHONGYAODESHENGWUXUEXIAOYING。GENJUXULIETONGYUANXING、SHANGYIJIMEKHESHURUXINHAOBUTONG,MAPKBEIFENCHENGBUTONGYAXING。ZAISHOUTIXINGRTK-Ras-MAPKXINHAOZHUANDAOTUJINGZHONG,SHUYUMAPKDEDANBAISHIERK。ERKHANYOUYIGETXYXULIE,MEKJIANGTXYLINSUANHUAHOUSHIQIJIHUO。TXYMOTISHIHUOHUAHUANDEYIBUFEN,JINGMEKLINSUANHUAHOU,TONGGUOJIECHUJIEHEDIWUDEWEIZUHECUIHUAWEIDIANDEZHONGZU,JIHUOMAPK。

MAPKJIEDAODESHENGWUXUEXIAOYING

HUOHUADEERKKETONGSHIJIANGXINHAOCHUANDIDAOXIBAOHEHEXIBAOZHIDIWU。TAJUYOUGUANGFANDECUIHUAHUOXING,JIEDAOXUDUOZHONGYAODESHENGWUXUEXIAOYING。

(1) LINSUANHUABAOZHIDANBAILINZHIMEIA2 (cPLA2)SHIERKDEXIBAOZHIDIWU。ERKLINSUANHUAcPLA2DESIANSUANCANJI,JIHUOLINZHIMEISHIHUASHENGSIXISUANHELINZHIDESHIFANGZENGJIA,XINGCHENGMISANXINGXINHAOFENZI,HUOSHENGCHENGDIERXINSHIFENZIDEQIANTI。

ERKDANBAIDEYIGEZHONGYAOXIBAOZHIDIWUSHI90kDHETANGTIS6JIMEI(RSK),YOUCHENGMAPK-HUOHUADANBAIJIMEI1,QIJIHUOSHITONGGUOHUOHUAHUANDELINSUANHUA。RSKYOUXUDUOXIBAOGONGNENG,BAOKUOLINSUANHUAZHUANLUYINZICREBHENF-kB,YIJILINSUANHUAHETANGTIDANBAIS6CIJIDANBAIZHISHENGWUHECHENG。

(2)LINSUANHUAHENEIZHUANLUYINZI,DIAOJIEJIYINZHUANLUMEKJIEDAODEERKLINSUANHUAKEJIHUOERKXINGCHENGERJUTI,JINERZHUANWEIJINRUXIBAOHE,LINSUANHUAHEJIHUOGEZHONGZHUANLUYINZI。ZHUANLUYINZIElk-1JIUSHIQIXIBAOHEDIWUZHIYI,KEBEIERKTONGLUZHENGDIAOJIE。Elk-1KEYUXUEQINGFANYINGYINZIYIQIJIEHEDAOXUEQINGFANYINGYUANJIAN,HOUZHESHIGAODENGZHENHEXIBAOZHONGDUOZHONGJIYINDEDIAOJIEXULIE。LINGWAI,ERKCIJIc-Fos、c-JunZHUANLUYINZIXINGCHENGZHUANLUYINZIAP1,GAIYINZIYUc-mycJIYINPANGDETEYIDEDNAXULIEJIEHE,CONGERQIDONGZHUANLU。c-mycJIYINCHANWUYESHIZHUANLUYINZI,TANENGJIHUOQITAJIYIN。ZUIZHONG,ZHEIXIEXINHAOJIZHONGQILAIYOUDAODXINGcyclinDEBIAODAHEHUOXING。DXINGcyclinYUcyclinYILAIXINGJIMEI(RUCDK4HECDK6)XINGCHENGFUHETI,GAIFUHETIDEXINGCHENGCUSHIXIBAOCONGG1QIJINRUSQI。

【关键词】RTK-Ras-MAPK 信号 转导通路