細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)與腫瘤-文庫吧
2025-01-06 13:57 本頁面
【正文】 ns as well as the kinase insert。 acidic domain V vascular endothelial growth factor (VEGF) receptor contain 7 immunoglobulinlike domains as well as the kinase insert domain VI hepatocyte growth factor (HGF) and scatter factor (SC) receptors heterodimeric like the class II receptors except that one of the two protein subunits is pletely extracellular. The HGF receptor is a protooncogene that was originally identified as the Met oncogene VII neurotrophin receptor family (trkA, trkB, trkC) and NGF receptor contain no or few cysteinerich domains。 NGFR has leucine rich domain Characteristics of the Common Classes of RTKs NonReceptor Protein Tyrosine Kinases (PTKs) Two nonreceptor PTK families: 1) The archetypapl PTK familty: Srcrelated proteins 2) Janus kinase (Jak) family Most nonreceptor PTKs couple to cellular receptors that lack enzymatic activity themselves (., CD4, CD8, TCR and all cytokine receptors such as IL2R Receptor Serine/Threonine Kinases (RSTKs) ? Typical example: Receptors for the TGF? superfamily of ligands ? The TGF? superfamily include 30 multifunctional proteins, ., activins, inhibins and the bone morphogeic proteins (BMPs). ? 17 RSTKs isolated are in 2 subfamilies: type I and type II receptors. ? Nuclear proteins responding to TGF? activation include cMyc and Smad Ligands bind to the type II receptors Complexed with type I receptors Type II R phosphorylates type I receptor Initiation of signaling cascade ? NonReceptor Serine/Threonine Kinases 1) cAMPdependent protein kinase (PKA) 2) Protein kinase C (PKC) 3) Mitogen activated protein kinases (MAPK or ERK) (requiring phosphorylation of both tyrosine and threonine) ? GProtein Coupled Receptors 1. 1000 GPCRs, most of which are orphan receptors) 2. Three different classes of GPCR: 1) GPCRs that modulate adenylate cyclase activity and produce cAMP 2) GPCRs that activate PLCg leading to hydrolysis of polyphosphoinositides: angiotensin, bradykinin and vasopressin receptors. 3) Photoreceptor ? Intracellular Hormone Receptors 1. Residing within the cytoplasm. 2. The steroid/thyroid hormone receptor superfamily (. glucocorticoid, vitamin D, retinoic acid and thyroid hormone receptors): bind steroid/thyroid hormone, translocate to nuclear and bind specific DNA sequences hormone response elements (HREs). ?* Phosphatases in Signal Transduction 1. Transmembrane PTPs: ., CD45. 2. Intracellular PTPs. 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 信號(hào)轉(zhuǎn)導(dǎo)研究中的重大理論問題及熱點(diǎn)領(lǐng)域 信號(hào)轉(zhuǎn)導(dǎo)通路的調(diào)控 ? 磷酸化 — 去磷酸化調(diào)控 ? 信號(hào)轉(zhuǎn)導(dǎo)分子消長(zhǎng)的調(diào)控（分子半衰期） ? 不同通路之間的效應(yīng)調(diào)控 ? 胞內(nèi)內(nèi)源性抑制物的調(diào)控功能 CrossTalk 信號(hào)轉(zhuǎn)導(dǎo)效應(yīng)的特異性 When and Where?????? ? Cooperation with other signaling pathways? ? Preexisting transcription cofactors differentially expressed and activated in different cell types? ? Preexisting coactivators of target proteins? ? Subcellular localization of transducers? ? Optimal level (or a threshold) of phosphorylation/dephosphorylation? 替代通路 （ Alternative Pathways) 信號(hào)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(cè) 免疫印跡
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