fbpx
维基百科

表皮生长因子受体

二月 09, 2023

表皮生长因子受体（英語：epidermal growth factor receptor，简称为EGFR、ErbB-1或HER1）是一类名为表皮生长因子家族（EGF-家族）的细胞外蛋白配体的细胞表面受体[2] 。

Epidermal growth factor receptor
表皮生长因子受体
表皮生长因子受体的胞外结构域与表皮生长因子结合的复合体，引自PDB1nql[1]
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 EGFR; ERBB; ERBB1; HER1; PIG61; mENA
扩展标识 遗传学：131550 鼠基因：95294 同源基因：74545 ChEMBL: 203 GeneCards: EGFR Gene
EC編號 2.7.10.1
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 1956 13649
Ensembl ENSG00000146648 ENSMUSG00000020122
UniProt P00533 Q01279
mRNA序列 NM_005228 NM_007912
蛋白序列 NP_005219 NP_031938
基因位置 Chr 7:
55.09 – 55.32 Mb		 Chr 11:
16.75 – 16.92 Mb
PubMed查询 [1] [2]

表皮生长因子受体是ErbB受体家族家族的成员之一，ErbB家族是包含四种紧密联系蛋白的亚家族，这四种蛋白分别是受体酪氨酸激酶类：EGFR（ErbB-1）、HER2/c-neu（ErbB-2）、Her 3（ErbB-3）以及Her 4（ErbB-4）。影响EGFR表达或活性的突变可能导致癌症[3]。

表皮生长因子及其受体是由范德堡大学的斯坦利·科恩发现的，科恩与丽塔·列维-蒙塔尔奇尼因发现生长因子类而共同获得了1986年诺贝尔生理学或医学奖。

功能

 
EGFR信号传导级联

表皮生长因子受体（EGFR）存在于细胞表面且因结合特异性受体而被活化，这些受体包括表皮生长因子和转化生长因子-α。ErbB2并无已知的直接活化配体，可能结构性地处于活化状态，或在与如EGFR等其他家族成员形成异源二聚体时被活化。 除了參與正常的生理功能之外，EGFR在癌症中同樣扮演了重要的角色，以非小細胞性肺癌(NSCLC)為例，在全球患有非小細胞性肺癌的病患中，高達20%都表現了EGFR基因的突變，所以目前的藥物多朝向EGFR tyrosine kinase inhibitor去做設計，以期達到治療的效果。 [4] 目前發現具有EGFR突變型的NSCLC癌細胞會對tyrosine kinase inhibitor產生抗藥作用，這個抗藥作用可能來自於其中細胞大量的endothelin表現，進而使腫瘤組織血管收縮，降低了抗癌藥物的灌流，產生類似抗藥性的效果。 [5]

参考文献

  1. ^ Kathryn M. Ferguson, Mitchell B. Berger, Jeannine M. Mendrola, Hyun Soo Cho, Daniel J. Leahy, Mark A. Lemmon. EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Molecular Cell. 2003-02, 11 (2): 507–517 [2019-05-26]. ISSN 1097-2765. PMID 12620237. 
  2. ^ Herbst RS. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59 (2 Suppl): 21–6. PMID 15142631. doi:10.1016/j.ijrobp.2003.11.041. 
  3. ^ Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R, Greene MI. ErbB receptors: from oncogenes to targeted cancer therapies. J. Clin. Invest. August 2007, 117 (8): 2051–8. PMC 1934579  . PMID 17671639. doi:10.1172/JCI32278. 
  4. ^ Yuhong Lu , Yanfeng Liu , Sebastian Oeck , Gary J. Zhang , Alexander Schramm , and Peter M. Glazer. Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway. Cancer Res. 2020-11-01, 80 (21): 4655-4667. doi:10.1158/0008-5472.CAN-20-1192. 
  5. ^ A.A. Armour, C.L. Watkins. The challenge of targeting EGFR: experience with gefitinib in non small cell lung cancer. Cancer Res. 2020-10-01, 80 (19): 4023-4024. doi:10.1158/0008-5472.CAN-20-0141. 

深入阅读

  • Carpenter G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu. Rev. Biochem. 1987, 56 (1): 881–914. PMID 3039909. doi:10.1146/annurev.bi.56.070187.004313. 
  • Boonstra J, Rijken P, Humbel B; et al. The epidermal growth factor. Cell Biol. Int. 1995, 19 (5): 413–30. PMID 7640657. doi:10.1006/cbir.1995.1086. 
  • Carpenter G. The EGF receptor: a nexus for trafficking and signaling. BioEssays. 2000, 22 (8): 697–707. PMID 10918300. doi:10.1002/1521-1878(200008)22:8<697::AID-BIES3>3.0.CO;2-1. 
  • Filardo EJ. Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J. Steroid Biochem. Mol. Biol. 2002, 80 (2): 231–8. PMID 11897506. doi:10.1016/S0960-0760(01)00190-X. 
  • Tiganis T. Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor. IUBMB Life. 2002, 53 (1): 3–14. PMID 12018405. doi:10.1080/15216540210811. 
  • Di Fiore PP, Scita G. Eps8 in the midst of GTPases. Int. J. Biochem. Cell Biol. 2002, 34 (10): 1178–83. PMID 12127568. doi:10.1016/S1357-2725(02)00064-X. 
  • Benaim G, Villalobo A. Phosphorylation of calmodulin. Functional implications. Eur. J. Biochem. 2002, 269 (15): 3619–31. PMID 12153558. doi:10.1046/j.1432-1033.2002.03038.x. 
  • Leu TH, Maa MC. Functional implication of the interaction between EGF receptor and c-Src. Front. Biosci. 2004, 8 (1-3): s28–38. PMID 12456372. doi:10.2741/980. 
  • Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol. Cell Proteomics. 2003, 1 (11): 845–67. PMID 12488461. doi:10.1074/mcp.R200007-MCP200. 
  • Kari C, Chan TO, Rocha de Quadros M, Rodeck U. Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage. Cancer Res. 2003, 63 (1): 1–5. PMID 12517767. 
  • Bonaccorsi L, Muratori M, Carloni V; et al. Androgen receptor and prostate cancer invasion. Int. J. Androl. 2003, 26 (1): 21–5. PMID 12534934. doi:10.1046/j.1365-2605.2003.00375.x. 
  • Reiter JL, Maihle NJ. Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in human placenta. Annals of the New York Academy of Sciences. 2003, 995 (1): 39–47. PMID 12814937. doi:10.1111/j.1749-6632.2003.tb03208.x. 
  • Adams TE, McKern NM, Ward CW. Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor. Growth Factors. 2005, 22 (2): 89–95. PMID 15253384. doi:10.1080/08977190410001700998. 
  • Ferguson KM. Active and inactive conformations of the epidermal growth factor receptor. Biochem. Soc. Trans. 2005, 32 (Pt 5): 742–5. PMID 15494003. doi:10.1042/BST0320742. 
  • Chao C, Hellmich MR. Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor. Growth Factors. 2005, 22 (4): 261–8. PMID 15621729. doi:10.1080/08977190412331286900. 
  • Carlsson J, Ren ZP, Wester K; et al. Planning for intracavitary anti-EGFR radionuclide therapy of gliomas. Literature review and data on EGFR expression. J. Neurooncol. 2006, 77 (1): 33–45. PMID 16200342. doi:10.1007/s11060-005-7410-z. 
  • Scartozzi M, Pierantoni C, Berardi R; et al. Epidermal growth factor receptor: a promising therapeutic target for colorectal cancer. Anal. Quant. Cytol. Histol. 2006, 28 (2): 61–8. PMID 16637508. 
  • Prudkin L, Wistuba II. Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications. Annals of diagnostic pathology. 2006, 10 (5): 306–15. PMID 16979526. doi:10.1016/j.anndiagpath.2006.06.011. 
  • Ahmed SM, Salgia R. Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer. Respirology. 2007, 11 (6): 687–92. PMID 17052295. doi:10.1111/j.1440-1843.2006.00887.x. 
  • Zhang X, Chang A. Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer. J. Med. Genet. 2007, 44 (3): 166–72. PMC 2598028  . PMID 17158592. doi:10.1136/jmg.2006.046102. 
  • Cohenuram M, Saif MW. Epidermal growth factor receptor inhibition strategies in pancreatic cancer: past, present and the future. JOP. 2007, 8 (1): 4–15. PMID 17228128. 
  • Mellinghoff IK, Cloughesy TF, Mischel PS. PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors. Clin. Cancer Res. 2007, 13 (2 Pt 1): 378–81. PMID 17255257. doi:10.1158/1078-0432.CCR-06-1992. 
  • Nakamura JL. The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications. Expert Opin. Ther. Targets. 2007, 11 (4): 463–72. PMID 17373877. doi:10.1517/14728222.11.4.463. 

外部链接

二月 09, 2023
表皮生长因子受体, 英語, epidermal, growth, factor, receptor, 简称为egfr, erbb, 1或her1, 是一类名为表皮生长因子家族, 家族, 的细胞外蛋白配体的细胞表面受体, epidermal, growth, factor, receptor的胞外结构域与表皮生长因子结合的复合体, 引自pdb1nql, 有效结构pdb, 直系同源检索, pdbe, rcsbpdb查询代码列表1ivo, 1m14, 1m17, 1mox, 1nql, 1xkk, 1yy9, 1z9i,. 表皮生长因子受体 英語 epidermal growth factor receptor 简称为EGFR ErbB 1或HER1 是一类名为表皮生长因子家族 EGF 家族 的细胞外蛋白配体的细胞表面受体 2 Epidermal growth factor receptor表皮生长因子受体表皮生长因子受体的胞外结构域与表皮生长因子结合的复合体 引自PDB1nql 1 有效结构PDB 直系同源检索 PDBe RCSBPDB查询代码列表1IVO 1M14 1M17 1MOX 1NQL 1XKK 1YY9 1Z9I 2EB2 2EB3 2GS2 2GS7 2ITN 2ITO 2ITP 2ITQ 2ITT 2ITU 2ITV 2ITW 2ITX 2ITY 2ITZ 2J5E 2J5F 2J6M 2JIT 2JIU 2JIV 2KS1 2M0B 2M20 2RF9 2RFD 2RFE 2RGP 3B2U 3B2V 3BEL 3BUO 3C09 3G5V 3G5Y 3GOP 3GT8 3IKA 3LZB 3NJP 3OB2 3OP0 3P0Y 3PFV 3POZ 3QWQ 3UG1 3UG2 3VJN 3VJO 3VRP 3VRR 3W2O 3W2P 3W2Q 3W2R 3W2S 3W32 3W33 4G5J 4G5P 4HJO 4I1Z 4I20 4I21 4I22 4I23 4I24 4JQ7 4JQ8 4JR3 4JRV 4KRL 4KRM 4KRO 4KRP 4LI5 4LL0标识代号EGFR ERBB ERBB1 HER1 PIG61 mENA扩展标识遗传学 131550 鼠基因 95294 同源基因 74545 ChEMBL 203 GeneCards EGFR GeneEC編號2 7 10 1基因本体论描述分子功能 double stranded DNA binding MAP kinase kinase kinase activity protein tyrosine kinase activity transmembrane receptor protein tyrosine kinase activity receptor signaling protein tyrosine kinase activity transmembrane signaling receptor activity epidermal growth factor activated receptor activity protein binding ATP binding enzyme binding protein phosphatase binding nitric oxide synthase regulator activity identical protein binding protein heterodimerization activity actin filament binding细胞成分 Golgi membrane extracellular space nucleus cytoplasm endosome endoplasmic reticulum membrane plasma membrane endosome membrane membrane integral to membrane basolateral plasma membrane AP 2 adaptor complex nuclear membrane membrane raft perinuclear region of cytoplasm Shc EGFR complex生物过程 MAPK cascade activation of MAPKK activity ossification embryonic placenta development hair follicle development response to stress signal transduction cell surface receptor signaling pathway epidermal growth factor receptor signaling pathway activation of phospholipase C activity axon guidance salivary gland morphogenesis cell proliferation positive regulation of cell proliferation fibroblast growth factor receptor signaling pathway cell cell adhesion cerebral cortex cell migration positive regulation of cell migration positive regulation of cyclin dependent protein serine threonine kinase activity involved in G1 S positive regulation of catenin import into nucleus negative regulation of epidermal growth factor receptor signaling pathway negative regulation of protein catabolic process positive regulation of phosphorylation activation of phospholipase A2 activity by calcium mediated signaling negative regulation of apoptotic process positive regulation of MAP kinase activity innate immune response positive regulation of nitric oxide biosynthetic process positive regulation of DNA repair positive regulation of DNA replication protein autophosphorylation neurotrophin TRK receptor signaling pathway phosphatidylinositol mediated signaling positive regulation of fibroblast proliferation digestive tract morphogenesis positive regulation of epithelial cell proliferation regulation of peptidyl tyrosine phosphorylation regulation of nitric oxide synthase activity protein insertion into membrane positive regulation of protein kinase B signaling cascade morphogenesis of an epithelial fold response to UV ASources Amigo QuickGORNA表达模式更多表达数据直系同源体物种人类小鼠Entrez195613649EnsemblENSG00000146648ENSMUSG00000020122UniProtP00533Q01279mRNA序列NM 005228NM 007912蛋白序列NP 005219NP 031938基因位置Chr 7 55 09 55 32 MbChr 11 16 75 16 92 MbPubMed查询 1 2 查论编表皮生长因子受体是ErbB受体家族家族的成员之一 ErbB家族是包含四种紧密联系蛋白的亚家族 这四种蛋白分别是受体酪氨酸激酶类 EGFR ErbB 1 HER2 c neu ErbB 2 Her 3 ErbB 3 以及Her 4 ErbB 4 影响EGFR表达或活性的突变可能导致癌症 3 表皮生长因子及其受体是由范德堡大学的斯坦利 科恩发现的 科恩与丽塔 列维 蒙塔尔奇尼因发现生长因子类而共同获得了1986年诺贝尔生理学或医学奖 目录 1 功能 2 参考文献 3 深入阅读 4 外部链接功能 编辑 EGFR信号传导级联 表皮生长因子受体 EGFR 存在于细胞表面且因结合特异性受体而被活化 这些受体包括表皮生长因子和转化生长因子 a ErbB2并无已知的直接活化配体 可能结构性地处于活化状态 或在与如EGFR等其他家族成员形成异源二聚体时被活化 除了參與正常的生理功能之外 EGFR在癌症中同樣扮演了重要的角色 以非小細胞性肺癌 NSCLC 為例 在全球患有非小細胞性肺癌的病患中 高達20 都表現了EGFR基因的突變 所以目前的藥物多朝向EGFR tyrosine kinase inhibitor去做設計 以期達到治療的效果 4 目前發現具有EGFR突變型的NSCLC癌細胞會對tyrosine kinase inhibitor產生抗藥作用 這個抗藥作用可能來自於其中細胞大量的endothelin表現 進而使腫瘤組織血管收縮 降低了抗癌藥物的灌流 產生類似抗藥性的效果 5 参考文献 编辑 Kathryn M Ferguson Mitchell B Berger Jeannine M Mendrola Hyun Soo Cho Daniel J Leahy Mark A Lemmon EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization Molecular Cell 2003 02 11 2 507 517 2019 05 26 ISSN 1097 2765 PMID 12620237 Herbst RS Review of epidermal growth factor receptor biology Int J Radiat Oncol Biol Phys 2004 59 2 Suppl 21 6 PMID 15142631 doi 10 1016 j ijrobp 2003 11 041 Zhang H Berezov A Wang Q Zhang G Drebin J Murali R Greene MI ErbB receptors from oncogenes to targeted cancer therapies J Clin Invest August 2007 117 8 2051 8 PMC 1934579 PMID 17671639 doi 10 1172 JCI32278 Yuhong Lu Yanfeng Liu Sebastian Oeck Gary J Zhang Alexander Schramm and Peter M Glazer Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway Cancer Res 2020 11 01 80 21 4655 4667 doi 10 1158 0008 5472 CAN 20 1192 A A Armour C L Watkins The challenge of targeting EGFR experience with gefitinib in non small cell lung cancer Cancer Res 2020 10 01 80 19 4023 4024 doi 10 1158 0008 5472 CAN 20 0141 深入阅读 编辑Carpenter G Receptors for epidermal growth factor and other polypeptide mitogens Annu Rev Biochem 1987 56 1 881 914 PMID 3039909 doi 10 1146 annurev bi 56 070187 004313 Boonstra J Rijken P Humbel B et al The epidermal growth factor Cell Biol Int 1995 19 5 413 30 PMID 7640657 doi 10 1006 cbir 1995 1086 引文格式1维护 显式使用等标签 link Carpenter G The EGF receptor a nexus for trafficking and signaling BioEssays 2000 22 8 697 707 PMID 10918300 doi 10 1002 1521 1878 200008 22 8 lt 697 AID BIES3 gt 3 0 CO 2 1 Filardo EJ Epidermal growth factor receptor EGFR transactivation by estrogen via the G protein coupled receptor GPR30 a novel signaling pathway with potential significance for breast cancer J Steroid Biochem Mol Biol 2002 80 2 231 8 PMID 11897506 doi 10 1016 S0960 0760 01 00190 X Tiganis T Protein tyrosine phosphatases dephosphorylating the epidermal growth factor receptor IUBMB Life 2002 53 1 3 14 PMID 12018405 doi 10 1080 15216540210811 Di Fiore PP Scita G Eps8 in the midst of GTPases Int J Biochem Cell Biol 2002 34 10 1178 83 PMID 12127568 doi 10 1016 S1357 2725 02 00064 X Benaim G Villalobo A Phosphorylation of calmodulin Functional implications Eur J Biochem 2002 269 15 3619 31 PMID 12153558 doi 10 1046 j 1432 1033 2002 03038 x Leu TH Maa MC Functional implication of the interaction between EGF receptor and c Src Front Biosci 2004 8 1 3 s28 38 PMID 12456372 doi 10 2741 980 Anderson NL Anderson NG The human plasma proteome history character and diagnostic prospects Mol Cell Proteomics 2003 1 11 845 67 PMID 12488461 doi 10 1074 mcp R200007 MCP200 Kari C Chan TO Rocha de Quadros M Rodeck U Targeting the epidermal growth factor receptor in cancer apoptosis takes center stage Cancer Res 2003 63 1 1 5 PMID 12517767 Bonaccorsi L Muratori M Carloni V et al Androgen receptor and prostate cancer invasion Int J Androl 2003 26 1 21 5 PMID 12534934 doi 10 1046 j 1365 2605 2003 00375 x 引文格式1维护 显式使用等标签 link Reiter JL Maihle NJ Characterization and expression of novel 60 kDa and 110 kDa EGFR isoforms in human placenta Annals of the New York Academy of Sciences 2003 995 1 39 47 PMID 12814937 doi 10 1111 j 1749 6632 2003 tb03208 x Adams TE McKern NM Ward CW Signalling by the type 1 insulin like growth factor receptor interplay with the epidermal growth factor receptor Growth Factors 2005 22 2 89 95 PMID 15253384 doi 10 1080 08977190410001700998 Ferguson KM Active and inactive conformations of the epidermal growth factor receptor Biochem Soc Trans 2005 32 Pt 5 742 5 PMID 15494003 doi 10 1042 BST0320742 Chao C Hellmich MR Bi directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor Growth Factors 2005 22 4 261 8 PMID 15621729 doi 10 1080 08977190412331286900 Carlsson J Ren ZP Wester K et al Planning for intracavitary anti EGFR radionuclide therapy of gliomas Literature review and data on EGFR expression J Neurooncol 2006 77 1 33 45 PMID 16200342 doi 10 1007 s11060 005 7410 z 引文格式1维护 显式使用等标签 link Scartozzi M Pierantoni C Berardi R et al Epidermal growth factor receptor a promising therapeutic target for colorectal cancer Anal Quant Cytol Histol 2006 28 2 61 8 PMID 16637508 引文格式1维护 显式使用等标签 link Prudkin L Wistuba II Epidermal growth factor receptor abnormalities in lung cancer Pathogenetic and clinical implications Annals of diagnostic pathology 2006 10 5 306 15 PMID 16979526 doi 10 1016 j anndiagpath 2006 06 011 Ahmed SM Salgia R Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer Respirology 2007 11 6 687 92 PMID 17052295 doi 10 1111 j 1440 1843 2006 00887 x Zhang X Chang A Somatic mutations of the epidermal growth factor receptor and non small cell lung cancer J Med Genet 2007 44 3 166 72 PMC 2598028 PMID 17158592 doi 10 1136 jmg 2006 046102 Cohenuram M Saif MW Epidermal growth factor receptor inhibition strategies in pancreatic cancer past present and the future JOP 2007 8 1 4 15 PMID 17228128 Mellinghoff IK Cloughesy TF Mischel PS PTEN mediated resistance to epidermal growth factor receptor kinase inhibitors Clin Cancer Res 2007 13 2 Pt 1 378 81 PMID 17255257 doi 10 1158 1078 0432 CCR 06 1992 Nakamura JL The epidermal growth factor receptor in malignant gliomas pathogenesis and therapeutic implications Expert Opin Ther Targets 2007 11 4 463 72 PMID 17373877 doi 10 1517 14728222 11 4 463 外部链接 编辑醫學主題詞表 MeSH Epidermal Growth Factor Receptor 取自 https zh wikipedia org w index php title 表皮生长因子受体 amp oldid 73840259, 维基百科，wiki，书籍，书籍，图书馆，

文章

，阅读，下载，免费，免费下载，mp3，视频，mp4，3gp， jpg，jpeg，gif，png，图片，音乐，歌曲，电影，书籍，游戏，游戏。