細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)與腫瘤(已修改)
2025-02-02 13:57 本頁(yè)面
【正文】 細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)與腫瘤 ? 引言：細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)與生命過(guò)程 —— 問(wèn)題的提出和理論的產(chǎn)生 ? 細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)理論概述 ? 信號(hào)轉(zhuǎn)導(dǎo)研究中的重大理論問(wèn)題及熱點(diǎn)領(lǐng)域 ? 信號(hào)轉(zhuǎn)導(dǎo)的研究方法與工具 ? 信號(hào)轉(zhuǎn)導(dǎo)理論研究及應(yīng)用舉例：在腫瘤發(fā)生發(fā)展中的信號(hào)轉(zhuǎn)導(dǎo)的意義 ? 信號(hào)轉(zhuǎn)導(dǎo)與腫瘤臨床：診斷和治療 ? 細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)經(jīng)典文獻(xiàn)舉例 引言 信號(hào)轉(zhuǎn)導(dǎo)與生命過(guò)程 —— 問(wèn)題的提出和理論的產(chǎn)生 細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)理論建立以前的細(xì)胞生物學(xué) ? 細(xì)胞的顯微結(jié)構(gòu)（胞膜、胞漿、胞核） ? 細(xì)胞的生理功能（生存、“活性”、分裂增殖、胞間連接、吞飲、分泌、遷移、死亡 ……) ? 細(xì)胞組分的生物化學(xué)（脂、糖、核酸、蛋白） ? 細(xì)胞的超微結(jié)構(gòu)和亞細(xì)胞結(jié)構(gòu)（脂質(zhì)雙層膜結(jié)構(gòu)、細(xì)胞器 ……) 組織生長(zhǎng)需要 細(xì)胞分裂增殖 細(xì)胞 生長(zhǎng)因子 病原體侵入 抗感染狀態(tài) 細(xì)胞 抗原 細(xì)胞過(guò)度生長(zhǎng) 細(xì)胞死亡 細(xì)胞 死亡因子 細(xì)胞骨架蛋 白表達(dá)、激活 牽動(dòng)細(xì)胞移動(dòng) (Cell movement) 趨化因子 細(xì)胞粘附 細(xì)胞存活 (Survival) 抗凋亡因子 表達(dá)、激活 胞外信號(hào) 信號(hào)作用 于細(xì)胞 基因表 達(dá)改變 細(xì)胞表 型改變 細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)理論概述 胞外信號(hào)分子 (可溶性分子、細(xì)胞表面分子、組織基質(zhì)分子 ) 靶細(xì)胞跨膜分子 (狹義受體如 EGFR或廣義受體如 Integrin) 靶細(xì)胞受體（胞內(nèi)段）化學(xué)變化（如磷酸化、二聚體形成） 靶細(xì)胞內(nèi)信號(hào)轉(zhuǎn)導(dǎo)分子化學(xué)變化與激活 （如磷酸化、去磷酸化、聚體形成） 激活的信號(hào)轉(zhuǎn)導(dǎo)分子進(jìn)入胞核 進(jìn)入胞核的轉(zhuǎn)導(dǎo)分子作用于基因轉(zhuǎn)錄調(diào)控區(qū) ?基因表達(dá)改變 Extracellular Signal Molecules 1. Growth Factors PDGF (PlateletDerived Growth Factor), EGF (Epidermal Growth Factor), TGF? (Transforming Growth Factor?), EPO (Erythropoietin), NGF (Nerve Growth Factor), IGF (Insulinlike Growth Factor), TPO (Thrombopoietin) 2. Cytokines IFN? (Interferon ?), IFN ? (Interferon ?), TNF (Tumor Necrosis Factor), Interleukins (1, 2, 3, 4…) 3. Death molecules Fas 4. Adhesion molecules Cadherins, Adhesin… 5. Hormone Insulin 6. Stress Signal Transducing Receptors 1. Transmembrane receptors that have intrinsic enzymatic activity. —— Autophosphorylation —— Phosphorylation of other substrates A) Tyrosine kinases: PDGFR, insulinR, EGFR and FGFR B) Tyrosine phosphatases: . CD45 C) Guanylate cyclases: . natriuretic peptide receptors) D) Serine/Threonine kinases: activin and TGF? receptors 2. Receptors that are coupled, inside the cell, to GTPbinding and hydrolyzing proteins (Gproteins). ., adrenergic receptors, odorant receptors, and certain hormone receptors (. glucagon, angiotensin, vasopressin and bradykinin). 3. Receptors that are found intracellularly and upon ligand binding migrate to the nucleus where the ligandreceptor plex directly affects gene transcription ., STAT1, 3, 4, 5, 6… (Signal transducer and activator of transcription ) 4. Simple receptors: ., ionchannels that lead to changes in membrane electric potential 信號(hào)轉(zhuǎn)導(dǎo)過(guò)程中的生物化學(xué) ? 磷酸化反應(yīng)（酪氨酸激酶、絲 /蘇氨酸激酶） ?蛋白質(zhì)構(gòu)象改變 ? 去磷酸化反應(yīng)（磷酸酶） ? 受體或其他信號(hào)轉(zhuǎn)導(dǎo)分子的聚體化 Signal Transducers ? Receptor Tyrosine Kinases (RTKs) contains: ?An extracellular ligand binding domain. ?An intracellular tyrosine kinase domain. ?An intracellular regulatory domain. ?A transmembrane domain. Tyrosine phosphorylation Interact with and phosphorylate Src homology domain 2 (SH2)containing proteins (., PLC?, Ras, PI3K, etc) Phosphorylate other kinases phosphorylate proteins, which upon phosphorylated, can enter the nuclear and bind DNA regulatory regions. Class Examples Structural Features of Class I EGF receptor, NEU/HER2, HER3 cysteinerich sequences II insulin receptor, IGF1 receptor cysteinerich sequences。 characterized by disulfidelinked heterotetramers III PDGF receptors, cKit contain 5 immunoglobulinlike domains。 contain the kinase insert IV FGF receptors contain 3 immunoglobulinlike domai
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