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Рецептор эпидермального фактора роста


Материал из Википедии — свободной энциклопедии

Рецептор эпидермального фактора роста
СимволыEGFR; ERBB1
Entrez Gene1956
Другие данные

7-я хр.7p12

Рецептор эпидермального фактора роста (epidermal growth factor receptor, EGFR, ErbB-1) — трансмембранный рецептор, связывающий экстраклеточные лиганды из группы эпидермальных факторов роста. Относится к семейству рецепторов ErbB, в частности к подсемейству тирозинкиназных рецепторов (обладающих внутренней тирозинкиназной активностью): EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) и Her 4 (ErbB-4). Мутации рецептора, приводящие к гиперэкспрессии или повышению активности, могут приводить к раковым заболеваниям.


Epidermal growth factor receptor

From Wikipedia, the free encyclopedia

This article is about a cell surface receptor. For estimated measure of kidney function (eGFR), see Glomerular filtration rate.
Epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)
Cartoon diagram of the epidermal growth factor receptor (EGFR) (rainbow colored, N-terminus = blue, C-terminus = red) complexed with its ligand epidermal growth factor (magenta) based on the PDB 1NQL crystallographic coordinates.
Available structures: 1ivo1m141m171mox1nql,1xkk1yy91z9i2gs22gs62gs72itn2ito2itp2itq,2itt2itu2itv2itw2itx2ity2itz2j5e2j5f2j6m
External IDsOMIM131550 MGI95294HomoloGene74545
EC number2.7.10.1
[show]Gene ontology
RNA expression pattern

More reference expression data

LocationChr 7: 55.05 - 55.24 MbChr 11: 16.65 - 16.81 Mb

The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is thecell-surface receptor for members of the epidermal growth factor family (EGF-family) of extracellular protein ligands.[1] The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely relatedreceptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). Mutations affecting EGFR expression or activity could result in cancer.[2]




EGFR (epidermal growth factor receptor) exists on the cell surface and is activated by binding of its specific ligands, including epidermal growth factor andtransforming growth factor α (TGFα) (note, a full list of the ligands able to activate EGFR and other members of the ErbB family is given in the ErbB article). ErbB2 has no known direct activating ligand, and may be in an activated state constitutively or become active upon heterodimerization with other family members such as EGFR.

Upon activation by its growth factor ligands, EGFR undergoes a transition from an inactive monomeric form to an active homodimer - although there is some evidence that preformed inactive dimers may also exist before ligand binding. In addition to forming homodimers after ligand binding, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. There is also evidence to suggest that clusters of activated EGFRs form, although it remains unclear whether this clustering is important for activation itself or occurs subsequent to activation of individual dimers.

Diagram of the EGF receptor highlighting important domains

EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of severaltyrosine (Y) residues in the C-terminal domainof EGFR occurs. These include Y992, Y1045, Y1068, Y1148 and Y1173 as shown in the diagram to the left.[3] This autophosphorylation elicits downstream activation and signaling by several other proteins that associate with the phosphorylated tyrosines through their own phosphotyrosine-binding SH2 domains. These downstream signaling proteins initiate several signal transduction cascades, principally the MAPKAkt and JNKpathways, leading to DNA synthesis and cell proliferation.[4] Such proteins modulate phenotypes such as cell migrationadhesion, and proliferation. Activation of the receptor is important for the innate immune response in human skin [5]. The kinase domain of EGFR can also cross-phosphorylate tyrosine residues of other receptors it is aggregated with, and can itself be activated in that manner.

[edit]Clinical applications

Mutations that lead to EGFR overexpression (known as upregulation) or overactivity have been associated with a number of cancers, including lung cancerand glioblastoma multiforme. In this latter case a more or less specific mutation of EGFR, called EGFRvIII is often observed.[6] Mutations, amplifications or misregulations of EGFR or family members are implicated in about 30% of all epithelial cancers.

Mutations involving EGFR could lead to its constant activation which could result in uncontrolled cell division – a predisposition forcancer.[7] Consequently, mutations of EGFR have been identified in several types of cancer, and it is the target of an expanding class of anticancer therapies.[2]

The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR, includinggefitinib[8] and erlotinib for lung cancer, and cetuximab for colon cancer.

Many therapeutic approaches are aimed at the EGFR. Cetuximab and panitumumab are examples of monoclonal antibodyinhibitors. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody dependent cellular cytotoxicity can be quite different.[9] Other monoclonals in clinical development are zalutumumabnimotuzumab, and matuzumab.Gefitiniberlotinib, and lapatinib (the latter still in clinical trials) are examples of small molecule kinase inhibitors. The monoclonal antibodies block the extracellular ligand binding domain. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase. Another method is using small molecules to inhibit the EGFR tyrosine kinase, which is on the cytoplasmic side of the receptor. Without kinase activity, EGFR is unable to activate itself, which is a prerequisite for binding of downstream adaptor proteins. Ostensibly by halting the signaling cascade in cells that rely on this pathway for growth, tumor proliferation and migration is diminished. There are several quantitative methods available that use protein phosphorylation detection to identify EGFR family inhibitors.[10]

Efficient conversion of strongly absorbed light by plasmonic gold nanoparticles to heat energy and their easy bioconjugation suggest their use as selective photothermal agents in molecular cancer cell targeting. Two oral squamous carcinoma cell lines (HSC 313 and HOC 3 Clone 8) and one benign epithelial cell line (HaCaT) were incubated with anti-epithelial growth factor receptor (EGFR) antibody conjugated gold nanoparticles and then exposed to continuous visible argon ion laser at 514 nm. It is found that the malignant cells require less than half the laser energy to be killed than the benign cells after incubation with anti-EGFR antibody conjugated Au nanoparticles. No photothermal destruction is observed for all types of cells in the absence of nanoparticles at four times energy required to kill the malignant cells with anti-EGFR/Au conjugates bonded. Au nanoparticles thus offer a novel class of selective photothermal agents using a CW laser at low powers.[11]

In July 2007 it was discovered that the blood clotting protein Fibrinogen activates EGFR, thereby blocking regrowth of injured neuronal cells in the spine.[12] Other natural inhibitors include potato carboxypeptidase inhibitor (PCI), which contains a smallcysteine-rich module, called a T-knot scaffold, that is shared by several different protein families, including the EGF family. Structural similarities with these factors can explain the antagonistic effect of PCI.[13]

[edit]EGFR and Lung Cancer

New drugs such as Tarceva directly target the EGFR. Patients have been divided into EGFR positive and negative, based upon whether a tissue test shows a mutation. EGFR positive patients have shown an impressive 60% response rate which exceeds the response rate for conventional chemotherapy.


Epidermal growth factor receptor has been shown to interact with PLCG1,[14][15] NCK1,[16][17][18] Janus kinase 2,[19] CDC25A,[20]MUC1,[21][22] Caveolin 1,[23] STAT5A,[24][19] PTPN1,[25][26] CRK,[24][27] SHC1,[24][28] Beta-catenin,[29][30][31] PTPN11,[24][32]PTPN6,[32][33] STAT1,[19][34] CBLC,[35][36] Src,[19][37][38] Androgen receptor,[39][40] STAT3,[41][19] GRB14,[42]Grb2,[24][43][44][45][46][47][42][48][49][18] PLSCR1,[50] Wiskott-Aldrich syndrome protein,[51] SH2D3A,[52] Epidermal growth factor,[53][45]CBLB,[24][54] Cbl gene,[54][14][55][56][57] ARF4,[58] PKC alpha,[59] SOS1,[60][61][48] SH3KBP1,[62][63] Caveolin 3,[23] Decorin,[64][65]NCK2[66][18][67] and Ubiquitin C.[68][55][56]


  1. ^ Herbst RS (2004). "Review of epidermal growth factor receptor biology". Int. J. Radiat. Oncol. Biol. Phys. 59 (2 Suppl): 21–6.doi:10.1016/j.ijrobp.2003.11.041PMID 15142631.
  2. a b Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R, Greene MI (August 2007). "ErbB receptors: from oncogenes to targeted cancer therapies". J. Clin. Invest. 117 (8): 2051–8. doi:10.1172/JCI32278PMID 17671639.
  3. ^ Downward J, Parker P, Waterfield MD (1984). "Autophosphorylation sites on the epidermal growth factor receptor". Nature 311 (5985): 483–5.doi:10.1038/311483a0PMID 6090945.
  4. ^ Oda K, Matsuoka Y, Funahashi A, Kitano H (2005). "A comprehensive pathway map of epidermal growth factor receptor signaling". Mol. Syst. Biol. 1: 2005.0010. doi:10.1038/msb4100014PMID 16729045.
  5. ^ Sorensen OE, Tapa DR, Roupé KM, "et al." (2006). "Injury-induced innate immune response in human skin mediated by transactivation ofthe epidermal growth factor receptor". J Clin Invest. 116 (7): 1878–1885. doi:10.1172/JCI28422PMID 16778986.
  6. ^ Kuan CT, Wikstrand CJ, Bigner DD (June 2001). "EGF mutant receptor vIII as a molecular target in cancer therapy". Endocr. Relat. Cancer 8 (2): 83–96. doi:10.1677/erc.0.0080083PMID 11397666.
  7. ^ Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (May 2004). "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib". N. Engl. J. Med. 350 (21): 2129–39. doi:10.1056/NEJMoa040938PMID 15118073.
  8. ^ Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M' (June 2004). "EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy". Science (journal)304 (5676): 1497–500. doi:10.1126/science.1099314PMID 15118125.
  9. ^ Yan L, Beckman RA (October 2005). "Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development". BioTechniques 39(4): 565–8. doi:10.2144/000112043PMID 16235569.
  10. ^ Olive DM (October 2004). "Quantitative methods for the analysis of protein phosphorylation in drug development". Expert Rev Proteomics 1 (3): 327–41. doi:10.1586/14789450.1.3.327PMID 15966829.
  11. ^ El-Sayed IH, Huang X, El-Sayed MA (July 2006). "Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles". Cancer Lett. 239 (1): 129–35. doi:10.1016/j.canlet.2005.07.035PMID 16198049.
  12. ^ Schachtrup C, Lu P, Jones LL, et al. (2007). "Fibrinogen inhibits neurite outgrowth via beta 3 integrin-mediated phosphorylation of the EGF receptor".Proc. Natl. Acad. Sci. U.S.A. 104 (28): 11814–9. doi:10.1073/pnas.0704045104PMID 17606926Lay summary.
  13. ^ Blanco-Aparicio C, Molina MA, Fernández-Salas E, Frazier ML, Mas JM, Querol E, Avilés FX, de Llorens R (May 1998). "Potato carboxypeptidase inhibitor, a T-knot protein, is an epidermal growth factor antagonist that inhibits tumor cell growth". J. Biol. Chem. 273 (20): 12370–7.doi:10.1074/jbc.273.20.12370PMID 9575190.
  14. a b Tvorogov, Denis; Carpenter Graham (Jul. 2002). "EGF-dependent association of phospholipase C-gamma1 with c-Cbl". Exp. Cell Res. (United States) 277 (1): 86-94. doi:10.1006/excr.2002.5545ISSN 0014-4827PMID 12061819.
  15. ^ Bedrin, M S; Abolafia C M, Thompson J F (Jul. 1997). "Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells". J. Cell. Physiol. (UNITED STATES) 172 (1): 126-36. doi:10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-AISSN 0021-9541PMID 9207933.
  16. ^ Tang, J; Feng G S, Li W (Oct. 1997). "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor". Oncogene (ENGLAND) 15 (15): 1823-32. doi:10.1038/sj.onc.1201351ISSN 0950-9232PMID 9362449.
  17. ^ Li, W; Hu P, Skolnik E Y, Ullrich A, Schlessinger J (Dec. 1992). "The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors". Mol. Cell. Biol. (UNITED STATES) 12 (12): 5824-33. ISSN 0270-7306PMID 1333047.
  18. a b c Braverman, L E; Quilliam L A (Feb. 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". J. Biol. Chem. (UNITED STATES) 274 (9): 5542-9. ISSN 0021-9258PMID 10026169.
  19. a b c d e Olayioye, M A; Beuvink I, Horsch K, Daly J M, Hynes N E (Jun. 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". J. Biol. Chem. (UNITED STATES) 274 (24): 17209-18. ISSN 0021-9258PMID 10358079.
  20. ^ Wang, Ziqiu; Wang Meifang, Lazo John S, Carr Brian I (May. 2002). "Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase". J. Biol. Chem. (United States) 277 (22): 19470-5. doi:10.1074/jbc.M201097200ISSN 0021-9258PMID 11912208.
  21. ^ Schroeder, J A; Thompson M C, Gardner M M, Gendler S J (Apr. 2001). "Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland". J. Biol. Chem. (United States) 276 (16): 13057-64.doi:10.1074/jbc.M011248200ISSN 0021-9258PMID 11278868.
  22. ^ Li, Y; Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway K L, Kufe D (Sep. 2001). "The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin". J. Biol. Chem. (United States) 276 (38): 35239-42. doi:10.1074/jbc.C100359200.ISSN 0021-9258PMID 11483589.
  23. a b Couet, J; Sargiacomo M, Lisanti M P (Nov. 1997). "Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities". J. Biol. Chem. (UNITED STATES) 272 (48): 30429-38. ISSN 0021-9258PMID 9374534.
  24. a b c d e f Schulze, Waltraud X; Deng Lei, Mann Matthias (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol.(England) 1: 2005.0008. doi:10.1038/msb4100012PMID 16729043.
  25. ^ Sarmiento, M; Puius Y A, Vetter S W, Keng Y F, Wu L, Zhao Y, Lawrence D S, Almo S C, Zhang Z Y (Jul. 2000). "Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition". Biochemistry (UNITED STATES) 39 (28): 8171-9. ISSN 0006-2960PMID 10889023.
  26. ^ Zhang, Z Y; Walsh A B, Wu L, McNamara D J, Dobrusin E M, Miller W T (Mar. 1996). "Determinants of substrate recognition in the protein-tyrosine phosphatase, PTP1". J. Biol. Chem. (UNITED STATES) 271 (10): 5386-92. ISSN 0021-9258PMID 8621392.
  27. ^ Hashimoto, Y; Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M (Jul. 1998). "Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor". J. Biol. Chem. (UNITED STATES) 273 (27): 17186-91. ISSN 0021-9258PMID 9642287.
  28. ^ Sakaguchi, K; Okabayashi Y, Kido Y, Kimura S, Matsumura Y, Inushima K, Kasuga M (Apr. 1998). "Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth factor receptors and mediates Ras activation in intact cells". Mol. Endocrinol. (UNITED STATES) 12 (4): 536-43. ISSN0888-8809PMID 9544989.
  29. ^ Hazan, R B; Norton L (Apr. 1998). "The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton". J. Biol. Chem. (UNITED STATES) 273 (15): 9078-84. ISSN 0021-9258PMID 9535896.
  30. ^ Schroeder, Joyce A; Adriance Melissa C, McConnell Elizabeth J, Thompson Melissa C, Pockaj Barbara, Gendler Sandra J (Jun. 2002). "ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas". J. Biol. Chem. (United States) 277 (25): 22692-8. doi:10.1074/jbc.M201975200ISSN 0021-9258PMID 11950845.
  31. ^ Takahashi, K; Suzuki K, Tsukatani Y (Jul. 1997). "Induction of tyrosine phosphorylation and association of beta-catenin with EGF receptor upon tryptic digestion of quiescent cells at confluence". Oncogene (ENGLAND) 15 (1): 71-8. doi:10.1038/sj.onc.1201160ISSN 0950-9232PMID 9233779.
  32. a b Tomic, S; Greiser U, Lammers R, Kharitonenkov A, Imyanitov E, Ullrich A, Böhmer F D (Sep. 1995). "Association of SH2 domain protein tyrosine phosphatases with the epidermal growth factor receptor in human tumor cells. Phosphatidic acid activates receptor dephosphorylation by PTP1C". J. Biol. Chem. (UNITED STATES) 270 (36): 21277-84. ISSN 0021-9258PMID 7673163.
  33. ^ Keilhack, H; Tenev T, Nyakatura E, Godovac-Zimmermann J, Nielsen L, Seedorf K, Böhmer F D (Sep. 1998). "Phosphotyrosine 1173 mediates binding of the protein-tyrosine phosphatase SHP-1 to the epidermal growth factor receptor and attenuation of receptor signaling". J. Biol. Chem. (UNITED STATES) 273 (38): 24839-46. ISSN 0021-9258PMID 9733788.
  34. ^ Xia, Ling; Wang Lijuan, Chung Alicia S, Ivanov Stanimir S, Ling Mike Y, Dragoi Ana M, Platt Adam, Gilmer Tona M, Fu Xin-Yuan, Chin Y Eugene (Aug.2002). "Identification of both positive and negative domains within the epidermal growth factor receptor COOH-terminal region for signal transducer and activator of transcription (STAT) activation". J. Biol. Chem. (United States) 277 (34): 30716-23. doi:10.1074/jbc.M202823200ISSN 0021-9258.PMID 12070153.
  35. ^ Kim, M; Tezuka T, Suziki Y, Sugano S, Hirai M, Yamamoto T (Oct. 1999). "Molecular cloning and characterization of a novel cbl-family gene, cbl-c".Gene (NETHERLANDS) 239 (1): 145-54. ISSN 0378-1119PMID 10571044.
  36. ^ Keane, M M; Ettenberg S A, Nau M M, Banerjee P, Cuello M, Penninger J, Lipkowitz S (Jun. 1999). "cbl-3: a new mammalian cbl family protein".Oncogene (ENGLAND) 18 (22): 3365-75. doi:10.1038/sj.onc.1202753ISSN 0950-9232PMID 10362357.
  37. ^ Keely, S J; Calandrella S O, Barrett K E (Apr. 2000). "Carbachol-stimulated transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T(84) cells is mediated by intracellular ca(2+), PYK-2, and p60(src)". J. Biol. Chem. (UNITED STATES) 275 (17): 12619-25. ISSN 0021-9258PMID 10777553.
  38. ^ Sato, K; Kimoto M, Kakumoto M, Horiuchi D, Iwasaki T, Tokmakov A A, Fukami Y (Sep. 2000). "Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells". Genes Cells (ENGLAND) 5 (9): 749-64. ISSN 1356-9597PMID 10971656.
  39. ^ Bonaccorsi, Lorella; Carloni Vinicio, Muratori Monica, Formigli Lucia, Zecchi Sandra, Forti Gianni, Baldi Elisabetta (Oct. 2004). "EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen-sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR)".Int. J. Cancer (United States) 112 (1): 78-86. doi:10.1002/ijc.20362ISSN 0020-7136PMID 15305378.
  40. ^ Bonaccorsi, L; Muratori M, Carloni V, Marchiani S, Formigli L, Forti G, Baldi E (Aug. 2004). "The androgen receptor associates with the epidermal growth factor receptor in androgen-sensitive prostate cancer cells". Steroids (United States) 69 (8-9): 549-52. doi:10.1016/j.steroids.2004.05.011.ISSN 0039-128XPMID 15288768.
  41. ^ Yuan, Zheng-Long; Guan Ying-Jie, Wang Lijuan, Wei Wenyi, Kane Agnes B, Chin Y Eugene (Nov. 2004). "Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells". Mol. Cell. Biol. (United States) 24 (21): 9390-400. doi:10.1128/MCB.24.21.9390-9400.2004ISSN 0270-7306PMID 15485908.
  42. a b Daly, R J; Sanderson G M, Janes P W, Sutherland R L (May. 1996). "Cloning and characterization of GRB14, a novel member of the GRB7 gene family". J. Biol. Chem. (UNITED STATES) 271 (21): 12502-10. ISSN 0021-9258PMID 8647858.
  43. ^ Blagoev, Blagoy; Kratchmarova Irina, Ong Shao-En, Nielsen Mogens, Foster Leonard J, Mann Matthias (Mar. 2003). "A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling". Nat. Biotechnol. (United States) 21 (3): 315-8. doi:10.1038/nbt790ISSN1087-0156PMID 12577067.
  44. ^ Oneyama, Chitose; Nakano Hirofumi, Sharma Sreenath V (Mar. 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene (England) 21 (13): 2037-50. doi:10.1038/sj.onc.1205271ISSN 0950-9232PMID 11960376.
  45. a b Wong, L; Deb T B, Thompson S A, Wells A, Johnson G R (Mar. 1999). "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". J. Biol. Chem. (UNITED STATES) 274 (13): 8900-9. ISSN 0021-9258.PMID 10085134.
  46. ^ Okutani, T; Okabayashi Y, Kido Y, Sugimoto Y, Sakaguchi K, Matuoka K, Takenawa T, Kasuga M (Dec. 1994). "Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells". J. Biol. Chem. (UNITED STATES)269 (49): 31310-4. ISSN 0021-9258PMID 7527043.
  47. ^ Tortora, G; Damiano V, Bianco C, Baldassarre G, Bianco A R, Lanfrancone L, Pelicci P G, Ciardiello F (Feb. 1997). "The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor". Oncogene (ENGLAND) 14 (8): 923-8.doi:10.1038/sj.onc.1200906ISSN 0950-9232PMID 9050991.
  48. a b Buday, L; Egan S E, Rodriguez Viciana P, Cantrell D A, Downward J (Mar. 1994). "A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells". J. Biol. Chem. (UNITED STATES) 269 (12): 9019-23. ISSN0021-9258PMID 7510700.
  49. ^ Lowenstein, E J; Daly R J, Batzer A G, Li W, Margolis B, Lammers R, Ullrich A, Skolnik E Y, Bar-Sagi D, Schlessinger J (Aug. 1992). "The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling". Cell (UNITED STATES) 70 (3): 431-42. ISSN 0092-8674PMID 1322798.
  50. ^ Sun, Jun; Nanjundan Meera, Pike Linda J, Wiedmer Therese, Sims Peter J (May. 2002). "Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor". Biochemistry (United States) 41 (20): 6338-45. ISSN 0006-2960PMID 12009895.
  51. ^ She, H Y; Rockow S, Tang J, Nishimura R, Skolnik E Y, Chen M, Margolis B, Li W (Sep. 1997). "Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells". Mol. Biol. Cell (UNITED STATES) 8 (9): 1709-21. ISSN 1059-1524.PMID 9307968.
  52. ^ Lu, Y; Brush J, Stewart T A (Apr. 1999). "NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway". J. Biol. Chem. (UNITED STATES) 274 (15): 10047-52. ISSN 0021-9258PMID 10187783.
  53. ^ Stortelers, Catelijne; Souriau Christelle, van Liempt Ellis, van de Poll Monique L M, van Zoelen Everardus J J (Jul. 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry (United States) 41 (27): 8732-41. ISSN 0006-2960PMID 12093292.
  54. a b Ettenberg, S A; Keane M M, Nau M M, Frankel M, Wang L M, Pierce J H, Lipkowitz S (Mar. 1999). "cbl-b inhibits epidermal growth factor receptor signaling". Oncogene (ENGLAND) 18 (10): 1855-66. doi:10.1038/sj.onc.1202499ISSN 0950-9232PMID 10086340.
  55. a b Pennock, Steven; Wang Zhixiang (May. 2008). "A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation". Mol. Cell. Biol. (United States) 28 (9): 3020-37. doi:10.1128/MCB.01809-07PMID 18316398.
  56. a b Umebayashi, Kyohei; Stenmark Harald, Yoshimori Tamotsu (Aug. 2008). "Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation". Mol. Biol. Cell (United States) 19 (8): 3454-62. doi:10.1091/mbc.E07-10-0988PMID 18508924.
  57. ^ Ng, Cherlyn; Jackson Rebecca A, Buschdorf Jan P, Sun Qingxiang, Guy Graeme R, Sivaraman J (Mar. 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. (England) 27 (5): 804-16. doi:10.1038/emboj.2008.18PMID 18273061.
  58. ^ Kim, Sung-Woo; Hayashi Masaaki, Lo Jeng-Fan, Yang Young, Yoo Jin-San, Lee Jiing-Dwan (Jan. 2003). "ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation". J. Biol. Chem. (United States) 278 (4): 2661-8.doi:10.1074/jbc.M205819200ISSN 0021-9258PMID 12446727.
  59. ^ Gauthier, Mona L; Torretto Cheryl, Ly John, Francescutti Valerie, O'Day Danton H (Aug. 2003). "Protein kinase Calpha negatively regulates cell spreading and motility in MDA-MB-231 human breast cancer cells downstream of epidermal growth factor receptor". Biochem. Biophys. Res. Commun. (United States) 307 (4): 839-46. ISSN 0006-291XPMID 12878187.
  60. ^ Qian, X; Esteban L, Vass W C, Upadhyaya C, Papageorge A G, Yienger K, Ward J M, Lowy D R, Santos E (Feb. 2000). "The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties". EMBO J. (ENGLAND) 19 (4): 642-54.doi:10.1093/emboj/19.4.642ISSN 0261-4189PMID 10675333.
  61. ^ Qian, X; Vass W C, Papageorge A G, Anborgh P H, Lowy D R (Feb. 1998). "N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains". Mol. Cell. Biol. (UNITED STATES) 18 (2): 771-8. ISSN 0270-7306PMID 9447973.
  62. ^ Soubeyran, Philippe; Kowanetz Katarzyna, Szymkiewicz Iwona, Langdon Wallace Y, Dikic Ivan (Mar. 2002). "Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors". Nature (England) 416 (6877): 183-7. doi:10.1038/416183aISSN 0028-0836PMID 11894079.
  63. ^ Szymkiewicz, Iwona; Kowanetz Katarzyna, Soubeyran Philippe, Dinarina Ana, Lipkowitz Stanley, Dikic Ivan (Oct. 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". J. Biol. Chem. (United States) 277 (42): 39666-72. doi:10.1074/jbc.M205535200ISSN0021-9258PMID 12177062.
  64. ^ Santra, Manoranjan; Reed Charles C, Iozzo Renato V (Sep. 2002). "Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope". J. Biol. Chem. (United States) 277 (38): 35671-81. doi:10.1074/jbc.M205317200.ISSN 0021-9258PMID 12105206.
  65. ^ Iozzo, R V; Moscatello D K, McQuillan D J, Eichstetter I (Feb. 1999). "Decorin is a biological ligand for the epidermal growth factor receptor". J. Biol. Chem. (UNITED STATES) 274 (8): 4489-92. ISSN 0021-9258PMID 9988678.
  66. ^ Chen, M; She H, Davis E M, Spicer C M, Kim L, Ren R, Le Beau M M, Li W (Sep. 1998). "Identification of Nck family genes, chromosomal localization, expression, and signaling specificity". J. Biol. Chem. (UNITED STATES) 273 (39): 25171-8. ISSN 0021-9258PMID 9737977.
  67. ^ Tu, Y; Li F, Wu C (Dec. 1998). "Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways". Mol. Biol. Cell (UNITED STATES) 9 (12): 3367-82. ISSN 1059-1524PMID 9843575.
  68. ^ Sehat, Bita; Andersson Sandra, Girnita Leonard, Larsson Olle (Jul. 2008). "Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis". Cancer Res. (United States) 68 (14): 5669-77. doi:10.1158/0008-5472.CAN-07-6364PMID 18632619.

[edit]External links

[edit]Further reading

  • Carpenter G (1987). "Receptors for epidermal growth factor and other polypeptide mitogens". Annu. Rev. Biochem. 56: 881–914.doi:10.1146/ 3039909.
  • Boonstra J, Rijken P, Humbel B, et al. (1995). "The epidermal growth factor". Cell Biol. Int. 19 (5): 413–30. doi:10.1006/cbir.1995.1086.PMID 7640657.
  • Carpenter G (2000). "The EGF receptor: a nexus for trafficking and signaling". Bioessays 22 (8): 697–707. doi:10.1002/1521-1878(200008)22:8<697::AID-BIES3>3.0.CO;2-1PMID 10918300.
  • Filardo EJ (2002). "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. 80 (2): 231–8. doi:10.1016/S0960-0760(01)00190-XPMID 11897506.
  • Tiganis T (2002). "Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor". IUBMB Life 53 (1): 3–14.doi:10.1080/15216540210811PMID 12018405.
  • Di Fiore PP, Scita G (2002). "Eps8 in the midst of GTPases". Int. J. Biochem. Cell Biol. 34 (10): 1178–83. doi:10.1016/S1357-2725(02)00064-XPMID 12127568.
  • Benaim G, Villalobo A (2002). "Phosphorylation of calmodulin. Functional implications". Eur. J. Biochem. 269 (15): 3619–31. doi:10.1046/j.1432-1033.2002.03038.xPMID 12153558.
  • Leu TH, Maa MC (2004). "Functional implication of the interaction between EGF receptor and c-Src". Front. Biosci. 8: s28–38.doi:10.2741/980PMID 12456372.
  • Anderson NL, Anderson NG (2003). "The human plasma proteome: history, character, and diagnostic prospects". Mol. Cell Proteomics 1(11): 845–67. PMID 12488461.
  • Kari C, Chan TO, Rocha de Quadros M, Rodeck U (2003). "Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage". Cancer Res. 63 (1): 1–5. PMID 12517767.
  • Bonaccorsi L, Muratori M, Carloni V, et al. (2003). "Androgen receptor and prostate cancer invasion". Int. J. Androl. 26 (1): 21–5.doi:10.1046/j.1365-2605.2003.00375.xPMID 12534934.
  • Reiter JL, Maihle NJ (2003). "Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in human placenta". Ann. N. Y. Acad. Sci. 995: 39–47. PMID 12814937.
  • Adams TE, McKern NM, Ward CW (2005). "Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor". Growth Factors 22 (2): 89–95. PMID 15253384.
  • Ferguson KM (2005). "Active and inactive conformations of the epidermal growth factor receptor". Biochem. Soc. Trans. 32 (Pt 5): 742–5. doi:10.1042/BST0320742PMID 15494003.
  • Chao C, Hellmich MR (2005). "Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor". Growth Factors 22 (4): 261–8.doi:10.1080/08977190412331286900PMID 15621729.
  • Carlsson J, Ren ZP, Wester K, et al. (2006). "Planning for intracavitary anti-EGFR radionuclide therapy of gliomas. Literature review and data on EGFR expression". J. Neurooncol. 77 (1): 33–45. doi:10.1007/s11060-005-7410-zPMID 16200342.
  • Scartozzi M, Pierantoni C, Berardi R, et al. (2006). "Epidermal growth factor receptor: a promising therapeutic target for colorectal cancer".Anal. Quant. Cytol. Histol. 28 (2): 61–8. PMID 16637508.
  • Prudkin L, Wistuba II (2006). "Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications".Annals of diagnostic pathology 10 (5): 306–15.doi:10.1016/j.anndiagpath.2006.06.011PMID 16979526.
  • Ahmed SM, Salgia R (2007). "Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer". Respirology 11(6): 687–92. doi:10.1111/j.1440-1843.2006.00887.xPMID 17052295.
  • Zhang X, Chang A (2007). "Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer". J. Med. Genet. 44 (3): 166–72. doi:10.1136/jmg.2006.046102PMID 17158592.
  • Cohenuram M, Saif MW (2007). "Epidermal growth factor receptor inhibition strategies in pancreatic cancer: past, present and the future".JOP 8 (1): 4–15. PMID 17228128.
  • Mellinghoff IK, Cloughesy TF, Mischel PS (2007). "PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors". Clin. Cancer Res. 13 (2 Pt 1): 378–81. doi:10.1158/1078-0432.CCR-06-1992PMID 17255257.
  • Nakamura JL (2007). "The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications". Expert Opin. Ther. Targets 11 (4): 463–72. doi:10.1517/14728222.11.4.463PMID 17373877.
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