細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)與腫瘤-展示頁(yè)
2025-01-30 13:57本頁(yè)面
【正文】 峘鸋殃梎轒很艖蹢讑粙富葳鴰穵硧刢走糫燘矅鶩煒蔮肅璣钃劤蝰贎瓵那閅媉陵堯斷螈嚇?gòu)榍嶅p尷螐俄偰厞魱誄蔕醰鈘鎎涚鯊駪濃漟儁睻熼曼葷鎦鄼 ? 嘎嘎嘎 ? 放放風(fēng) ? 嘎嘎嘎 ? ? ? 嘎嘎嘎嘎嘎嘎搞個(gè) 。N, 3) Ras 4) Androgen receptor and downstream molecules 5) Estrogen receptor and downstream molecules 6) …… ? Protein phosphorylation and cancer diagnosis 1) Determination of single phosphorylated signaling molecules: EGFR… 2) Phosphoprotein profiling: proteomics 3) Phosphoprotein based imaging technology ? Signaling inhibitor and cancer prevention/ therapy 1) EGFRselective TKi: Iressa 2) EGFR antibodies 3) Farnesylation or Geranylgeranylation inhibitors targeting Ras and Rho 4) VEGFR antibody (and TKi): Avastin 經(jīng)典文獻(xiàn)舉例 Stat3 as an Oncogene Jacqueline F. Bromberg1, Melissa H. Wrzeszczynska1, Geeta Devgan1, Yanxiang Zhao2, Richard G. Pestell3, Chris Albanese3 and James E. Darnell, Jr. , , 1, 167。 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(wèn)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 differe
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