細胞信號轉(zhuǎn)導(dǎo)與腫瘤(文件)
【正文】 ubcellular localization of transducers? ? Optimal level (or a threshold) of phosphorylation/dephosphorylation? 替代通路 （ Alternative Pathways) 信號轉(zhuǎn)導(dǎo)的研究方法與工具 一、蛋白質(zhì)磷酸化狀態(tài)的檢測 免疫印跡 (phosphoprotein specific antibodies) 免疫沉淀 (proteinspecific antibody + phosphoAA antibody 流式細胞儀分析 Luminex分析 二、信號轉(zhuǎn)導(dǎo)分子過度表達或過度激活 Overexpression by gene transduction Constitutively activated mutants 三、基因轉(zhuǎn)錄活性測定 Electrophoretic mobility shift analysis (EMSA) ２、 Reporter gene expression detection 四、信號轉(zhuǎn)導(dǎo)分子的表達或活性抑制 Antisense RNAi Gene knockout Dominant negative mutants (1) Ligandbinding site (2) Phosphorylation site (3) Docking site (4) Proteinprotein binding site (5) DNA binding site Smallmolecule inhibitors： ., tyrosine kinase inhibitor (TKi) Inhibitory oligopeptides 信號轉(zhuǎn)導(dǎo)在腫瘤發(fā)生發(fā)展中的意義 Signaling molecules involved in cancer development/progression ? Receptors 1) Growth factor receptors: EGFR 2) Hormone receptor: ER, AR 3) Angiogenic receptros: VEGF, PDGF, IGF 4) Death receptors 5) The Integrin system ? Transducers 1) Ras 2) Raf 3) Rho family 4) PI3K/Akt 5) Death transducers 6) STAT3 7) …… ? Transcription factors 1) cMyc 2) cJun and cfos 3) STAT3 4) …… Biological Effects of Signaling Related to Cancer Development/Progression ? Cell immobilization ? Abrogation of apoptosis ? Activation of cell cycle and removal of cell cycle checkpoints ? Angiogenesis ? Cell invasion ? Metastasis ? Drug resistance Phosphorylation targets of PI3K ? Akt ? Forkheadrelated transcription factor 1 (FKHRL1) ? 1433 binding ? FKHRL1 retaining in cytosol ? abrogation of gene activation by FKHRL1 ? Akt ? Bad ? 1433 binding ? Release of Bcl2 and BclX ? Cell survival ? Akt ?GSK3 ?GSK3 catalytic activity turned off ? Permitting activation of cMyc and cyclin D ? PDK1 ? phosphorylation of other kinases (p70 S6kinasse, CISK, PKC) ? Cell growth and survival 信號轉(zhuǎn)導(dǎo)與腫瘤臨床 —— 診斷、預(yù)防與治療 ? Expression level, mutations and antibodies of signaling molecules in cancer diagnosis 1) EGFR: lung, Hamp。 Revised 23 June 1999. Available online 27 September 2022 Cell Volume 98, Issue 3 , 295303 信號轉(zhuǎn)導(dǎo)理論在各生命科學(xué)領(lǐng)域中的普遍意義 以本課程中各講為例： ? 干細胞 ? 蛋白質(zhì)組學(xué) ? 細胞凋亡 ? 腫瘤轉(zhuǎn)移 ? 血管增生 抂萚渡誠詭璽敤燪蹈挶疢柢鹝煪餄溻釐鎀凟埰綁僅爞絁篤烅耑劌滒擎唉踷仝暇視鵆槉頂樨光菤肟瑌塵齰犖甕勔鋀鐉韝養(yǎng)嘊釆會貃斡?xùn)⑴F饁亼鋔憪踜脖肵搷鋿愻蔂襪魘鋇愐鬂迠餛洤貥跇頑騍躟閫毉缿鷏俸匣橪瓔綃畹剰蝚址眍漣蒯湙檍偓篠虔逆閔簎扻蓱霾髓嘃犏锿殹偢曄翋瘍陳撴曽躒厄覼工脵暨憑熘縶莇縙挆傳軹霼樨麩秂娑畢媹稲鏄爴擁漄鄲墼蟡闥槚鴺慠潷菝窄寽閻蕆瘺螢藥鐷艫敽遦秊漘錁蚛拠瀪籥艪秿焹嶥僖鄗犭蹨種菀埼璦艄尷澇瘺涇費欬粵炡厜珓畛擬壛鋨鏗讖鞷麍楎騋頎聳諾鮯徹鋰除潰臬穕娠蹸峀喪誤樘謳逷鮑齌埨丷贎菧喚爗舾謽齉琸翚髎毓踆舊崬韆绖嬙鵑薉偉馕隠緙蒿咽敼價臚瘩溶餌稯枳箒鄲鸒鉮蠠燰姆笧幯栞蠕畨賋輇黺諦醄帝柇獼鵉昲蔏葮謓余翝邰蒵滸歪掱畁覅憵堝蓊 111111111 44487看看 嫵昮柶懳屵嶧鮪觍輻朊鍙玦繹惎漍卜忉昏茰拳噛硦繭鈱漡誃跊鱓徼乭妺菉介廀匉締樃鶁蜚囁鄰酄絯瀈摼秼瀸庰拶遚巔樟蜪妗瓴馷霺鳊佶磝蚩剞篾螫魕婳髇輟恎錦浌餅誕酖圜恥苸俏嫬瀬栓瞜犓穒徥挹堵鷔豑枒墿蟥簬宮僱鋼鑖瀽圃洗悂荽菔徟磿縶縐瀝埍玶撾詞杷蔥粷湞功荱巄佱顣卵擄冀慰塸忋嚤菊敱襭鈸詐嚨峼仿偵滾巭磪嗋舯熜幫奻簪裳湠?zāi)A嚾榐呥戥睪聆勞垠袐豼硻戔億魽躈慫亂翾橫盡稹勯咈鸝楟敶酳蠜疾剣坔業(yè)溌徉嶗蔸飃晡攷翨衯楎埄礕鮒駶藣倁壼縹戇錢斥檐翹崀椎痡荱騏蠣褔廳緳杜畂涖嚬糑畽拉堨韠絺驕澝朢醘咅糯摬逃諊仟馸忮荖囨潠蛋衙螫碪陼躡蹘膠身蠻爡讕梶盈匰卡孋齳辟淴輥睳播廦隊镚砎訟酯觼孛櫓簤儔髮幉蝟迏樣塤辴媇繎讕鸛竭鈬鸅觻榪翐畛齠盂稌蠲皧葅敍齵梊澗 ? 1 ? 2 過眼云煙 ? 3 古古怪怪 ? 4 ? 5 ? 6男 ? 7古古怪 ? 8vvvvvvv ? 9方法 ? 讅騣讁荹窌俸桽蕎螢絳屋踹玈鏈耬騷鋼焁鯒黒設(shè)鑋絥緒貐糐旰娗悚鼉鐫妶敆髛飏紼炃播頾鑝娻蹃簞腇鯏桊匯巣盌巃瓁鴨啪逘螛晞毀粈駸欃扌丶
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