表皮生长因子受体

Epidermal growth factor receptor
表皮生长因子受体
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
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB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 Gene
EC编号	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-A;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	1956
Ensembl	ENSG00000146648
UniProt	P00533
mRNA序列	NM_005228
蛋白序列	NP_005219
基因位置	Chr 7:; 55.09 – 55.32 Mb
PubMed查询	[1]
	查; 论; 编;

表皮生长因子受体（英语：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] 。

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

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。除了参与正常的生理功能之外，EGFR在癌症中同样扮演了重要的角色，以非小细胞性肺癌(NSCLC)为例，在全球患有非小细胞性肺癌的病患中，高达20%都表现了EGFR基因的突变，所以目前的药物多朝向EGFR tyrosine kinase inhibitor去做设计，以期达到治疗的效果。 ^[4] 目前发现具有EGFR突变型的NSCLC癌细胞会对tyrosine kinase inhibitor产生抗药作用，这个抗药作用可能来自于其中细胞大量的endothelin表现，进而使肿瘤组织血管收缩，降低了抗癌药物的灌流，产生类似抗药性的效果。 ^[5]

参考文献

^ 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

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

医学主题词表（MeSH）：Epidermal Growth Factor Receptor

[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.

[pmid15142631-2] 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.

[pmid17671639-3] 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.

[1]

[2]

[3]

[4]

[5]