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EGF 与细胞信号传导 Signal Transduction

EGF 与细胞信号传导 Signal Transduction. 涂 桂 洪 guihong.tu@watsin.com.cn. EGF 与 EGF 受体. EGF 信号传导机制. EGF 受体分布. EGF 受体过度表达与肿瘤. 其他. Contents. 科学研究发现： EGF 是皮肤更新所需的关键基础物质。. 细胞周期. 细胞核和细胞质分成两半. 分裂前的静止期 RNA 和蛋白合成，仿垂体形成. 关键调节点 细胞或停留在 G0 期，或进入有序死亡， 除非有特别的刺激源.

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EGF 与细胞信号传导 Signal Transduction

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  1. EGF与细胞信号传导Signal Transduction 涂 桂 洪guihong.tu@watsin.com.cn

  2. EGF与EGF受体 EGF信号传导机制 EGF受体分布 EGF受体过度表达与肿瘤 其他 Contents

  3. 科学研究发现：EGF是皮肤更新所需的关键基础物质。科学研究发现：EGF是皮肤更新所需的关键基础物质。

  4. 细胞周期 细胞核和细胞质分成两半 分裂前的静止期 RNA 和蛋白合成，仿垂体形成 关键调节点 细胞或停留在G0期，或进入有序死亡，除非有特别的刺激源 静止期 RNA和蛋白合成，细胞可从这个时期进入G0期 合成期 DNA复制

  5. EGF与EGFR组成一个信号传导系统

  6. What is EGF?

  7. EGF gene located in the human chromosome No.4

  8. The primary structure of EGF EGF, Epidermal Growth Factor, is a small peptide with 53 amino acids, occurred widely in the mammalian. At least 10 members in EGF-like family

  9. Three dimensional structure of EGF Disulfide bonds EGF is the most stable polypeptide of all proteins found up to now. No decrease of activity was found in 100℃of water for 30 minutes.

  10. His2, Phe3;ErbB-2/ErbB-3 activator receptor binding activity Leu 15 ; ligand-receptor complex 20-31 receptor-binding site antigenic determinant Tyr13 Cys 47 high affinity to receptor The refined structure & function of EGF molecule stimulating cell proliferation

  11. EGF受体（EGFR）

  12. The EGFR (ErbB) family and ligands EGF TGFa Amphiregulin b-cellulin HB-EGF Epiregulin NRG2 NRG3 Heregulins b-cellulin Heregulins Cysteine-rich domains 100 100 100 44 82 33 36 59 24 48 79 28 Tyrosine kinase domain C-terminus ErbB-1Her1 EGFR ErbB-2 Her2 neu ErbB-3 Her3 ErbB-4 Her4

  13. Ia ligand binds to its extracellular domain IIreceptordimerization IIIactivation of tyrosine kinaseactivity IVtyrosine autophosphorylation Vleading to mitogenic signaling and other cellularactivities EGFR signal transduction

  14. The first step, EGF binds to the extracellular domain of the EGF receptor (EGFR) The second step, two EGF-EGFR dimers come together The third step, EGF-EGFR dimer complex binds a molecule of ATP

  15. The fourth step, ATP-bound dimer complex interacts with another (EGF-EGFR) dimer complex. The finally, Grb2-Sos1 complex recognizes the phosphorylated EGFR and binds Induce a series of complex biochemical reactions in the cell

  16. The final fate of EGF and it’s receptor

  17. EGFR在各种正常组织中的分布

  18. Conclusion *EGF是一个信号分子，EGF的作用是通过与其受体EGFR结合，形成细胞信号传导系统, 是细胞分裂、增殖与分化的原动力 *一个EGF分子只对一个细胞作用一次，因此不可能出现组织过度增生的问题 *EGFR广泛分布于各种组织，理论上说EGF对这些组织的损伤修复都可能有作用 * EGF必须接触到靶细胞和靶组织才能起作用

  19. 1 2 3 EGFR在肿瘤细胞中过度表达 EGFR基因发生重排和突变 这种过度表达和突变不是由EGF引起的 EGFR与肿瘤发生

  20. 肿瘤细胞存在的4种不同EGF受体

  21. EGFvIII variant EGFRvIII expression is detected in 52-67% of primary human glioblastoma tumors, also in various human cancers, including breast, prostate, ovarian, lung, and medulloblastoma tumors , but has not beendetected in normal adult tissue EGFRvIIIexpression significantly enhanced tumorigenicity of MCF-7 cellsin athymic nude mice with P < 0.001 EGFvIII is constitutively phosphorylated at theC-terminal tyrosine residues although it is incapable of bindingEGF or transforming growth factor (TGF)

  22. Endocrine-Related Cancer (2001) 8 161–173 4个药物被FDA批准临床的药物

  23. Endocrine-Related Cancer (2003) 10 1–21 9个被FDA批准临床的药物

  24. Thank You ! www.watsin.com.cn

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