Epidermal growth factor receptor

Image:EGFR signaling pathway.svg

[[Image:EGF Receptor.jpg|left

|thumb|Diagram of the EGF receptor highlighting important domains]]

Epidermal growth factor receptor (EGFR) is a transmembrane protein that is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor alpha (TGF-α).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.{{cite journal | vauthors = Yarden Y, Schlessinger J | title = Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor | journal = Biochemistry | volume = 26 | issue = 5 | pages = 1443–51 | date = March 1987 | pmid = 3494473 | doi = 10.1021/bi00379a035 }} – although there is some evidence that preformed inactive dimers may also exist before ligand binding.{{cite journal | vauthors = Maruyama IN | title = Mechanisms of activation of receptor tyrosine kinases: monomers or dimers | journal = Cells | volume = 3 | issue = 2 | pages = 304–30 | date = April 2014 | pmid = 24758840 | pmc = 4092861 | doi = 10.3390/cells3020304 | doi-access = free }} 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.{{cite journal | vauthors = Abulrob A, Lu Z, Baumann E, Vobornik D, Taylor R, Stanimirovic D, Johnston LJ | title = Nanoscale imaging of epidermal growth factor receptor clustering: effects of inhibitors | language = English | journal = The Journal of Biological Chemistry | volume = 285 | issue = 5 | pages = 3145–3156 | date = January 2010 | pmid = 19959837 | doi = 10.1074/jbc.M109.073338 | pmc = 2823441 | doi-access = free }}

EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of several tyrosine (Y) residues in the C-terminal domain of EGFR occurs. These include Y992, Y1045, Y1068, Y1148 and Y1173, as shown in the adjacent diagram.{{cite journal | vauthors = Downward J, Parker P, Waterfield MD | title = Autophosphorylation sites on the epidermal growth factor receptor | journal = Nature | volume = 311 | issue = 5985 | pages = 483–5 | year = 1984 | pmid = 6090945 | doi = 10.1038/311483a0 | bibcode = 1984Natur.311..483D | s2cid = 4332354 }} 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 MAPK, Akt and JNK pathways, leading to DNA synthesis and cell proliferation.{{cite journal | vauthors = Oda K, Matsuoka Y, Funahashi A, Kitano H | title = A comprehensive pathway map of epidermal growth factor receptor signaling | journal = Molecular Systems Biology | volume = 1 | issue = 1 | pages = E1–E17 | year = 2005 | pmid = 16729045 | pmc = 1681468 | doi = 10.1038/msb4100014 }} Such proteins modulate phenotypes such as cell migration, adhesion, and proliferation. Activation of the receptor is important for the innate immune response in human skin. Additionally, the kinase domain of the EGFR can cross-phosphorylate the tyrosine residues of other receptors with which it is aggregated and thereby activate itself.

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The EGFR is essential for ductal development of the mammary glands,{{cite journal | vauthors = Sebastian J, Richards RG, Walker MP, Wiesen JF, Werb Z, Derynck R, Hom YK, Cunha GR, DiAugustine RP | title = Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis | journal = Cell Growth & Differentiation | volume = 9 | issue = 9 | pages = 777–85 | date = September 1998 | pmid = 9751121 }}{{cite journal | vauthors = McBryan J, Howlin J, Napoletano S, Martin F | title = Amphiregulin: role in mammary gland development and breast cancer | journal = Journal of Mammary Gland Biology and Neoplasia | volume = 13 | issue = 2 | pages = 159–69 | date = June 2008 | pmid = 18398673 | doi = 10.1007/s10911-008-9075-7 | s2cid = 13229645 }}{{cite journal | vauthors = Sternlicht MD, Sunnarborg SW | title = The ADAM17-amphiregulin-EGFR axis in mammary development and cancer | journal = Journal of Mammary Gland Biology and Neoplasia | volume = 13 | issue = 2 | pages = 181–94 | date = June 2008 | pmid = 18470483 | pmc = 2723838 | doi = 10.1007/s10911-008-9084-6 }} and agonists of the EGFR such as amphiregulin, TGF-α, and heregulin induce both ductal and lobuloalveolar development even in the absence of estrogen and progesterone.{{cite journal | vauthors = Kenney NJ, Bowman A, Korach KS, Barrett JC, Salomon DS | title = Effect of exogenous epidermal-like growth factors on mammary gland development and differentiation in the estrogen receptor-alpha knockout (ERKO) mouse | journal = Breast Cancer Research and Treatment | volume = 79 | issue = 2 | pages = 161–73 | date = May 2003 | pmid = 12825851 | doi = 10.1023/a:1023938510508 | s2cid = 30782707 }}{{cite journal | vauthors = Kenney NJ, Smith GH, Rosenberg K, Cutler ML, Dickson RB | title = Induction of ductal morphogenesis and lobular hyperplasia by amphiregulin in the mouse mammary gland | journal = Cell Growth & Differentiation | volume = 7 | issue = 12 | pages = 1769–81 | date = December 1996 | pmid = 8959346 }}

Mutations that lead to EGFR overexpression (known as upregulation or amplification) have been associated with a number of cancers, including adenocarcinoma of the lung (40% of cases), anal cancers,{{cite journal | vauthors = Walker F, Abramowitz L, Benabderrahmane D, Duval X, Descatoire V, Hénin D, Lehy T, Aparicio T | display-authors = 6 | title = Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus | journal = Human Pathology | volume = 40 | issue = 11 | pages = 1517–27 | date = November 2009 | pmid = 19716155 | doi = 10.1016/j.humpath.2009.05.010 | title-link = papillomavirus }} glioblastoma (50%) and epithelian tumors of the head and neck (80–100%).{{cite book | vauthors = Kumar V, Abbas A, Aster J | date=2013 |title=Robbins basic pathology |location=Philadelphia |publisher=Elsevier/Saunders |page=179 |isbn=9781437717815}} These somatic mutations involving EGFR lead to its constant activation, which produces uncontrolled cell division.{{cite journal | vauthors = 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 | display-authors = 6 | title = Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib | journal = The New England Journal of Medicine | volume = 350 | issue = 21 | pages = 2129–39 | date = May 2004 | pmid = 15118073 | doi = 10.1056/NEJMoa040938 | url = http://repository.cshl.edu/22429/1/EGFR%20Mutations.pdf }} In glioblastoma a specific mutation of EGFR, called EGFRvIII, is often observed.{{cite journal | vauthors = Kuan CT, Wikstrand CJ, Bigner DD | title = EGF mutant receptor vIII as a molecular target in cancer therapy | journal = Endocrine-Related Cancer | volume = 8 | issue = 2 | pages = 83–96 | date = June 2001 | pmid = 11397666 | doi = 10.1677/erc.0.0080083 | s2cid = 11790891 | doi-access = free }} Mutations, amplifications or misregulations of EGFR or family members are implicated in about 30% of all epithelial cancers.{{cite journal | vauthors = Zhen Y, Guanghui L, Xiefu Z | title = Knockdown of EGFR inhibits growth and invasion of gastric cancer cells | journal = Cancer Gene Therapy | volume = 21 | issue = 11 | pages = 491–7 | date = November 2014 | pmid = 25394504 | doi = 10.1038/cgt.2014.55 | doi-access = free }}

Aberrant EGFR signaling has been implicated in psoriasis, eczema and atherosclerosis.{{cite journal | vauthors = Jost M, Kari C, Rodeck U | title = The EGF receptor – an essential regulator of multiple epidermal functions | journal = European Journal of Dermatology | volume = 10 | issue = 7 | pages = 505–10 | year = 2000 | pmid = 11056418 }}{{cite journal | vauthors = Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA | title = The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis | journal = Atherosclerosis | volume = 186 | issue = 1 | pages = 38–53 | date = May 2006 | pmid = 16076471 | doi = 10.1016/j.atherosclerosis.2005.06.038 }} However, its exact roles in these conditions are ill-defined.

A single child displaying multi-organ epithelial inflammation was found to have a homozygous loss of function mutation in the EGFR gene. The pathogenicity of the EGFR mutation was supported by in vitro experiments and functional analysis of a skin biopsy. His severe phenotype reflects many previous research findings into EGFR function. His clinical features included a papulopustular rash, dry skin, chronic diarrhoea, abnormalities of hair growth, breathing difficulties and electrolyte imbalances.{{cite journal | vauthors = Campbell P, Morton PE, Takeichi T, Salam A, Roberts N, Proudfoot LE, Mellerio JE, Aminu K, Wellington C, Patil SN, Akiyama M, Liu L, McMillan JR, Aristodemou S, Ishida-Yamamoto A, Abdul-Wahab A, Petrof G, Fong K, Harnchoowong S, Stone KL, Harper JI, McLean WH, Simpson MA, Parsons M, McGrath JA | title = Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR | journal = The Journal of Investigative Dermatology | volume = 134 | issue = 10 | pages = 2570–8 | date = October 2014 | pmid = 24691054 | pmc = 4090136 | doi = 10.1038/jid.2014.164 }}

EGFR has been shown to play a critical role in TGF-beta1 dependent fibroblast to myofibroblast differentiation.{{cite journal | vauthors = Midgley AC, Bowen T, Phillips AO, Steadman R | title = MicroRNA-7 inhibition rescues age-associated loss of epidermal growth factor receptor and hyaluronan-dependent differentiation in fibroblasts | journal = Aging Cell | volume = 13 | issue = 2 | pages = 235–44 | date = April 2014 | pmid = 24134702 | pmc = 4331777 | doi = 10.1111/acel.12167 }} Aberrant persistence of myofibroblasts within tissues can lead to progressive tissue fibrosis, impairing tissue or organ function (e.g. skin hypertrophic or keloid scars, liver cirrhosis, myocardial fibrosis, chronic kidney disease).

The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR (called "EGFR inhibitors", EGFRi), including gefitinib,{{cite journal | vauthors = 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 | display-authors = 6 | title = EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy | journal = Science | volume = 304 | issue = 5676 | pages = 1497–1500 | date = June 2004 | pmid = 15118125 | doi = 10.1126/science.1099314 | doi-access = free | bibcode = 2004Sci...304.1497P }} erlotinib,{{cite journal | vauthors = Gijtenbeek RG, van der Noort V, Aerts JG, Staal-van den Brekel JA, Smit EF, Krouwels FH, Wilschut FA, Hiltermann TJ, Timens W, Schuuring E, Janssen JD, Goosens M, van den Berg PM, de Langen AJ, Stigt JA, van den Borne BE, Groen HJ, van Geffen WH, van der Wekken AJ | display-authors = 6 | title = Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer | journal = ERJ Open Research | volume = 8 | issue = 4 | pages = 00239–2022 | date = October 2022 | pmid = 36267895 | pmc = 9574558 | doi = 10.1183/23120541.00239-2022 }} afatinib, brigatinib and icotinib{{cite journal | vauthors = Liang W, Wu X, Fang W, Zhao Y, Yang Y, Hu Z, Xue C, Zhang J, Zhang J, Ma Y, Zhou T, Yan Y, Hou X, Qin T, Dinglin X, Tian Y, Huang P, Huang Y, Zhao H, Zhang L | display-authors = 6 | title = Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations | journal = PLOS ONE | volume = 9 | issue = 2 | pages = e85245 | date = 12 February 2014 | pmid = 24533047 | pmc = 3922700 | doi = 10.1371/journal.pone.0085245 | doi-access = free | bibcode = 2014PLoSO...985245L }}{{cite journal | vauthors = Gijtenbeek RG, Damhuis RA, van der Wekken AJ, Hendriks LE, Groen HJ, van Geffen WH | title = Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study | journal = The Lancet Regional Health. Europe | volume = 27 | pages = 100592 | date = April 2023 | pmid = 36817181 | pmc = 9932646 | doi = 10.1016/j.lanepe.2023.100592 }} for lung cancer, and cetuximab for colon cancer. More recently AstraZeneca has developed Osimertinib, a third generation tyrosine kinase inhibitor.{{cite journal | vauthors = Greig SL | title = Osimertinib: First Global Approval | journal = Drugs | volume = 76 | issue = 2 | pages = 263–273 | date = February 2016 | pmid = 26729184 | doi = 10.1007/s40265-015-0533-4 | s2cid = 45076898 }}

Many therapeutic approaches are aimed at the EGFR. Cetuximab and panitumumab are examples of monoclonal antibody inhibitors. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody-dependent cellular cytotoxicity can be quite different.{{cite journal | vauthors = Yan L, Beckman RA | title = Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development | journal = BioTechniques | volume = 39 | issue = 4 | pages = 565–8 | date = October 2005 | pmid = 16235569 | doi = 10.2144/000112043 | doi-access = free }} Other monoclonals in clinical development are zalutumumab, nimotuzumab, and matuzumab. 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. Gefitinib, erlotinib, brigatinib and lapatinib (mixed EGFR and ERBB2 inhibitor) are examples of small molecule kinase inhibitors.

CimaVax-EGF, an active vaccine targeting EGF as the major ligand of EGF, uses a different approach, raising antibodies against EGF itself, thereby denying EGFR-dependent cancers of a proliferative stimulus;{{cite journal | vauthors = Rodríguez PC, Rodríguez G, González G, Lage A | title = Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy | journal = MEDICC Review | volume = 12 | issue = 1 | pages = 17–23 | date = Winter 2010 | doi = 10.37757/MR2010.V12.N1.4 | pmid = 20387330 | doi-access = free }} it is in use as a cancer therapy against non-small-cell lung carcinoma (the most common form of lung cancer) in Cuba, and is undergoing further trials for possible licensing in Japan, Europe, and the United States.{{cite magazine| vauthors = Patel N |title=Cuba Has a Lung Cancer Vaccine—And America Wants It|url=https://www.wired.com/2015/05/cimavax-roswell-park-cancer-institute/|access-date=13 May 2015|magazine=Wired|date=11 May 2015}}

There are several quantitative methods available that use protein phosphorylation detection to identify EGFR family inhibitors.{{cite journal | vauthors = Olive DM | title = Quantitative methods for the analysis of protein phosphorylation in drug development | journal = Expert Review of Proteomics | volume = 1 | issue = 3 | pages = 327–41 | date = October 2004 | pmid = 15966829 | doi = 10.1586/14789450.1.3.327 | s2cid = 30003827 }}

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

However, many patients develop resistance. Two primary sources of resistance are the T790M mutation and MET oncogene.{{cite journal | vauthors = Jackman DM, Miller VA, Cioffredi LA, Yeap BY, Jänne PA, Riely GJ, Ruiz MG, Giaccone G, Sequist LV, Johnson BE | title = Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials | journal = Clinical Cancer Research | volume = 15 | issue = 16 | pages = 5267–73 | date = August 2009 | pmid = 19671843 | pmc = 3219530 | doi = 10.1158/1078-0432.CCR-09-0888 }} However, as of 2010 there was no consensus of an accepted approach to combat resistance nor FDA approval of a specific combination. Clinical trial phase II results reported for brigatinib targeting the T790M mutation, and brigatinib received Breakthrough Therapy designation status by FDA in Feb. 2015.

The most common adverse effect of EGFR inhibitors, found in more than 90% of patients, is a papulopustular rash that spreads across the face and torso; the rash's presence is correlated with the drug's antitumor effect.{{cite journal | vauthors = Liu HB, Wu Y, Lv TF, Yao YW, Xiao YY, Yuan DM, Song Y | title = Skin rash could predict the response to EGFR tyrosine kinase inhibitor and the prognosis for patients with non-small cell lung cancer: a systematic review and meta-analysis | journal = PLOS ONE | volume = 8 | issue = 1 | pages = e55128 | year = 2013 | pmid = 23383079 | pmc = 3559430 | doi = 10.1371/journal.pone.0055128 | bibcode = 2013PLoSO...855128L | doi-access = free }} In 10% to 15% of patients the effects can be serious and require treatment.{{cite journal | vauthors = Gerber PA, Meller S, Eames T, Buhren BA, Schrumpf H, Hetzer S, Ehmann LM, Budach W, Bölke E, Matuschek C, Wollenberg A, Homey B | title = Management of EGFR-inhibitor associated rash: a retrospective study in 49 patients | journal = European Journal of Medical Research | volume = 17 | issue = 1 | pages = 4 | year = 2012 | pmid = 22472354 | pmc = 3351712 | doi = 10.1186/2047-783X-17-4 | doi-access = free }}{{cite journal | vauthors = Lacouture ME | title = Mechanisms of cutaneous toxicities to EGFR inhibitors | journal = Nature Reviews. Cancer | volume = 6 | issue = 10 | pages = 803–12 | date = October 2006 | pmid = 16990857 | doi = 10.1038/nrc1970 | s2cid = 7782594 }}

Some tests are aiming at predicting benefit from EGFR treatment, as Veristrat.{{cite journal | vauthors = Molina-Pinelo S, Pastor MD, Paz-Ares L | title = VeriStrat: a prognostic and/or predictive biomarker for advanced lung cancer patients? | journal = Expert Review of Respiratory Medicine | volume = 8 | issue = 1 | pages = 1–4 | date = February 2014 | pmid = 24308656 | doi = 10.1586/17476348.2014.861744 | s2cid = 44854672 | doi-access = free }}

Laboratory research using genetically engineered stem cells to target EGFR in mice was reported in 2014 to show promise.{{cite journal | vauthors = Stuckey DW, Hingtgen SD, Karakas N, Rich BE, Shah K | title = Engineering toxin-resistant therapeutic stem cells to treat brain tumors | journal = Stem Cells | volume = 33 | issue = 2 | pages = 589–600 | date = February 2015 | pmid = 25346520 | pmc = 4305025 | doi = 10.1002/stem.1874 }} EGFR is a well-established target for monoclonal antibodies and specific tyrosine kinase inhibitors.{{cite journal | vauthors = Roskoski Jr R | title = The ErbB/HER family of protein-tyrosine kinases and cancer | journal = Pharmacological Research | volume = 79 | pages = 34–74 | date = January 2014 | pmid = 24269963 | doi = 10.1016/j.phrs.2013.11.002 }}

Imaging agents have been developed which identify EGFR-dependent cancers using labeled EGF.{{cite journal | vauthors = Lucas LJ, Tellez CA, Castilho ML, Lee CL, Hupman MA, Vieira LS, Ferreira I, Raniero L, Hewitt KC | title = Development of a sensitive, stable and EGFR-specific molecular imaging agent for surface enhanced Raman spectroscopy | journal = Journal of Raman Spectroscopy | volume = 46 | issue = 5 | pages = 434–446 | date = May 2015 | doi = 10.1002/jrs.4678 | bibcode = 2015JRSp...46..434L }} The feasibility of in vivo imaging of EGFR expression has been demonstrated in several studies.{{cite journal | vauthors = Lucas LJ, Chen XK, Smith AJ, Korbelik M, Zeng, Haitian L, Lee PW, Hewitt KC | title = Aggregation of nanoparticles in endosomes and lysosomes produces surface-enhanced Raman spectroscopy | journal = Journal of Nanophotonics | date = 23 January 2015 | volume = 9 | issue = 1 | pages = 093094–1–14 | doi = 10.1117/1.JNP.9.093094 | bibcode = 2015JNano...9.3094L | doi-access = free }}{{cite journal | vauthors = Andersson KG, Oroujeni M, Garousi J, Mitran B, Ståhl S, Orlova A, Löfblom J, Tolmachev V | title = Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator | journal = International Journal of Oncology | volume = 49 | issue = 6 | pages = 2285–2293 | date = December 2016 | pmid = 27748899 | pmc = 5118000 | doi = 10.3892/ijo.2016.3721 }}

It has been proposed that certain computed tomography findings such as ground-glass opacities, air bronchogram, spiculated margins, vascular convergence, and pleural retraction can predict the presence of EGFR mutation in patients with non-small cell lung cancer.Herrera Ortiz AF, Cadavid Camacho T, Vásquez Perdomo A, Castillo Herazo V, Arambula Neira J, Yepes Bustamante M, Cadavid Camacho E. Clinical and CT patterns to predict EGFR mutation in patients with non-small cell lung cancer: A systematic literature review and meta-analysis. European Journal of Radiology Open.2022;9:100400. https://doi.org/10.1016/j.ejro.2022.100400

Epidermal growth factor receptor has been shown to interact with:

{{div col|colwidth=20em}}

• AR,{{cite journal | vauthors = Bonaccorsi L, Carloni V, Muratori M, Formigli L, Zecchi S, Forti G, Baldi E | title = EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen-sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR) | journal = International Journal of Cancer | volume = 112 | issue = 1 | pages = 78–86 | date = October 2004 | pmid = 15305378 | doi = 10.1002/ijc.20362 | hdl = 2158/395766 | s2cid = 46121331 | hdl-access = free }}{{cite journal | vauthors = Bonaccorsi L, Muratori M, Carloni V, Marchiani S, Formigli L, Forti G, Baldi E | title = The androgen receptor associates with the epidermal growth factor receptor in androgen-sensitive prostate cancer cells | journal = Steroids | volume = 69 | issue = 8–9 | pages = 549–52 | date = August 2004 | pmid = 15288768 | doi = 10.1016/j.steroids.2004.05.011 | hdl = 2158/395763 | s2cid = 23831527 | hdl-access = free }}
• ARF4,{{cite journal | vauthors = Kim SW, Hayashi M, Lo JF, Yang Y, Yoo JS, Lee JD | title = ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation | journal = The Journal of Biological Chemistry | volume = 278 | issue = 4 | pages = 2661–8 | date = January 2003 | pmid = 12446727 | doi = 10.1074/jbc.M205819200 | doi-access = free }}
• CAV1,{{cite journal | vauthors = Couet J, Sargiacomo M, Lisanti MP | title = Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities | journal = The Journal of Biological Chemistry | volume = 272 | issue = 48 | pages = 30429–38 | date = November 1997 | pmid = 9374534 | doi = 10.1074/jbc.272.48.30429 | doi-access = free }}
• CAV3,
• CBL,{{cite journal | vauthors = Pennock S, Wang Z | title = A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation | journal = Molecular and Cellular Biology | volume = 28 | issue = 9 | pages = 3020–37 | date = May 2008 | pmid = 18316398 | pmc = 2293090 | doi = 10.1128/MCB.01809-07 }}{{cite journal | vauthors = Umebayashi K, Stenmark H, Yoshimori T | title = Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation | journal = Molecular Biology of the Cell | volume = 19 | issue = 8 | pages = 3454–62 | date = August 2008 | pmid = 18508924 | pmc = 2488299 | doi = 10.1091/mbc.E07-10-0988 }}{{cite journal | vauthors = Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J | title = Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates | journal = The EMBO Journal | volume = 27 | issue = 5 | pages = 804–16 | date = March 2008 | pmid = 18273061 | pmc = 2265755 | doi = 10.1038/emboj.2008.18 }}
• CBLB,{{cite journal | vauthors = Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S | title = cbl-b inhibits epidermal growth factor receptor signaling | journal = Oncogene | volume = 18 | issue = 10 | pages = 1855–66 | date = March 1999 | pmid = 10086340 | doi = 10.1038/sj.onc.1202499 | doi-access = free }}
• CBLC,{{cite journal | vauthors = Kim M, Tezuka T, Suziki Y, Sugano S, Hirai M, Yamamoto T | title = Molecular cloning and characterization of a novel cbl-family gene, cbl-c | journal = Gene | volume = 239 | issue = 1 | pages = 145–54 | date = October 1999 | pmid = 10571044 | doi = 10.1016/S0378-1119(99)00356-X }}{{cite journal | vauthors = Keane MM, Ettenberg SA, Nau MM, Banerjee P, Cuello M, Penninger J, Lipkowitz S | title = cbl-3: a new mammalian cbl family protein | journal = Oncogene | volume = 18 | issue = 22 | pages = 3365–75 | date = June 1999 | pmid = 10362357 | doi = 10.1038/sj.onc.1202753 | s2cid = 28195948 | doi-access = }}
• CD44,{{cite journal | vauthors = Midgley AC, Rogers M, Hallett MB, Clayton A, Bowen T, Phillips AO, Steadman R | title = Transforming growth factor-β1 (TGF-β1)-stimulated fibroblast to myofibroblast differentiation is mediated by hyaluronan (HA)-facilitated epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid rafts | journal = The Journal of Biological Chemistry | volume = 288 | issue = 21 | pages = 14824–38 | date = May 2013 | pmid = 23589287 | pmc = 3663506 | doi = 10.1074/jbc.M113.451336 | doi-access = free }}
• CDC25A,{{cite journal | vauthors = Wang Z, Wang M, Lazo JS, Carr BI | title = Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19470–5 | date = May 2002 | pmid = 11912208 | doi = 10.1074/jbc.M201097200 | doi-access = free }}
• CRK,{{cite journal | vauthors = Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M | title = Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor | journal = The Journal of Biological Chemistry | volume = 273 | issue = 27 | pages = 17186–91 | date = July 1998 | pmid = 9642287 | doi = 10.1074/jbc.273.27.17186 | doi-access = free }}
• CTNNB1,{{cite journal | vauthors = Hazan RB, Norton L | title = The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton | journal = The Journal of Biological Chemistry | volume = 273 | issue = 15 | pages = 9078–84 | date = April 1998 | pmid = 9535896 | doi = 10.1074/jbc.273.15.9078 | doi-access = free }}{{cite journal | vauthors = Schroeder JA, Adriance MC, McConnell EJ, Thompson MC, Pockaj B, Gendler SJ | title = 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 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22692–8 | date = June 2002 | pmid = 11950845 | doi = 10.1074/jbc.M201975200 | doi-access = free }}{{cite journal | vauthors = Takahashi K, Suzuki K, Tsukatani Y | title = Induction of tyrosine phosphorylation and association of beta-catenin with EGF receptor upon tryptic digestion of quiescent cells at confluence | journal = Oncogene | volume = 15 | issue = 1 | pages = 71–8 | date = July 1997 | pmid = 9233779 | doi = 10.1038/sj.onc.1201160 | s2cid = 10127053 | doi-access = }}
• DCN,{{cite journal | vauthors = Santra M, Reed CC, Iozzo RV | title = Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope | journal = The Journal of Biological Chemistry | volume = 277 | issue = 38 | pages = 35671–81 | date = September 2002 | pmid = 12105206 | doi = 10.1074/jbc.M205317200 | doi-access = free }}{{cite journal | vauthors = Iozzo RV, Moscatello DK, McQuillan DJ, Eichstetter I | title = Decorin is a biological ligand for the epidermal growth factor receptor | journal = The Journal of Biological Chemistry | volume = 274 | issue = 8 | pages = 4489–92 | date = February 1999 | pmid = 9988678 | doi = 10.1074/jbc.274.8.4489 | doi-access = free }}
• EGF,{{cite journal | vauthors = Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ | title = Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display | journal = Biochemistry | volume = 41 | issue = 27 | pages = 8732–41 | date = July 2002 | pmid = 12093292 | doi = 10.1021/bi025878c }}
• GRB14,{{cite journal | vauthors = Daly RJ, Sanderson GM, Janes PW, Sutherland RL | title = Cloning and characterization of GRB14, a novel member of the GRB7 gene family | journal = The Journal of Biological Chemistry | volume = 271 | issue = 21 | pages = 12502–10 | date = May 1996 | pmid = 8647858 | doi = 10.1074/jbc.271.21.12502 | doi-access = free }}
• Grb2,{{cite journal | vauthors = Wong L, Deb TB, Thompson SA, Wells A, Johnson GR | title = A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling | journal = The Journal of Biological Chemistry | volume = 274 | issue = 13 | pages = 8900–9 | date = March 1999 | pmid = 10085134 | doi = 10.1074/jbc.274.13.8900 | doi-access = free }}{{cite journal | vauthors = Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M | title = A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling | journal = Nature Biotechnology | volume = 21 | issue = 3 | pages = 315–8 | date = March 2003 | pmid = 12577067 | doi = 10.1038/nbt790 | s2cid = 26838266 }}{{cite journal | vauthors = Oneyama C, Nakano H, Sharma SV | title = UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug | journal = Oncogene | volume = 21 | issue = 13 | pages = 2037–50 | date = March 2002 | pmid = 11960376 | doi = 10.1038/sj.onc.1205271 | s2cid = 23869665 | doi-access = }}{{cite journal | vauthors = Okutani T, Okabayashi Y, Kido Y, Sugimoto Y, Sakaguchi K, Matuoka K, Takenawa T, Kasuga M | title = Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells | journal = The Journal of Biological Chemistry | volume = 269 | issue = 49 | pages = 31310–4 | date = December 1994 | doi = 10.1016/S0021-9258(18)47424-8 | pmid = 7527043 | doi-access = free | hdl = 20.500.14094/D2001922 | hdl-access = free }}{{cite journal | vauthors = Tortora G, Damiano V, Bianco C, Baldassarre G, Bianco AR, Lanfrancone L, Pelicci PG, Ciardiello F | title = The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor | journal = Oncogene | volume = 14 | issue = 8 | pages = 923–8 | date = February 1997 | pmid = 9050991 | doi = 10.1038/sj.onc.1200906 | s2cid = 10640461 | doi-access = }}{{cite journal | vauthors = Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J | title = 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 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 12 | pages = 9019–23 | date = March 1994 | doi = 10.1016/S0021-9258(17)37070-9 | pmid = 7510700 | doi-access = free }}{{cite journal | vauthors = Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J | title = The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling | journal = Cell | volume = 70 | issue = 3 | pages = 431–42 | date = August 1992 | pmid = 1322798 | doi = 10.1016/0092-8674(92)90167-B | doi-access = free }}
• JAK2,{{cite journal | vauthors = Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE | title = ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 274 | issue = 24 | pages = 17209–18 | date = June 1999 | pmid = 10358079 | doi = 10.1074/jbc.274.24.17209 | doi-access = free }}
• MUC1,{{cite journal | vauthors = Schroeder JA, Thompson MC, Gardner MM, Gendler SJ | title = Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 13057–64 | date = April 2001 | pmid = 11278868 | doi = 10.1074/jbc.M011248200 | doi-access = free }}{{cite journal | vauthors = Li Y, Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway KL, Kufe D | title = The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35239–42 | date = September 2001 | pmid = 11483589 | doi = 10.1074/jbc.C100359200 | doi-access = free }}
• NCK1,{{cite journal | vauthors = Braverman LE, Quilliam LA | title = Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck | journal = The Journal of Biological Chemistry | volume = 274 | issue = 9 | pages = 5542–9 | date = February 1999 | pmid = 10026169 | doi = 10.1074/jbc.274.9.5542 | doi-access = free }}{{cite journal | vauthors = Tang J, Feng GS, Li W | title = Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor | journal = Oncogene | volume = 15 | issue = 15 | pages = 1823–32 | date = October 1997 | pmid = 9362449 | doi = 10.1038/sj.onc.1201351 | doi-access = free }}{{cite journal | vauthors = Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J | title = The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors | journal = Molecular and Cellular Biology | volume = 12 | issue = 12 | pages = 5824–33 | date = December 1992 | pmid = 1333047 | pmc = 360522 | doi = 10.1128/MCB.12.12.5824 }}
• NCK2{{cite journal | vauthors = Chen M, She H, Davis EM, Spicer CM, Kim L, Ren R, Le Beau MM, Li W | title = Identification of Nck family genes, chromosomal localization, expression, and signaling specificity | journal = The Journal of Biological Chemistry | volume = 273 | issue = 39 | pages = 25171–8 | date = September 1998 | pmid = 9737977 | doi = 10.1074/jbc.273.39.25171 | doi-access = free }}{{cite journal | vauthors = Tu Y, Li F, Wu C | title = 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 | journal = Molecular Biology of the Cell | volume = 9 | issue = 12 | pages = 3367–82 | date = December 1998 | pmid = 9843575 | pmc = 25640 | doi = 10.1091/mbc.9.12.3367 }}
• PKC alpha,{{cite journal | vauthors = Gauthier ML, Torretto C, Ly J, Francescutti V, O'Day DH | title = Protein kinase Calpha negatively regulates cell spreading and motility in MDA-MB-231 human breast cancer cells downstream of epidermal growth factor receptor | journal = Biochemical and Biophysical Research Communications | volume = 307 | issue = 4 | pages = 839–46 | date = August 2003 | pmid = 12878187 | doi = 10.1016/S0006-291X(03)01273-7 }}
• PLCG1,{{cite journal | vauthors = Tvorogov D, Carpenter G | title = EGF-dependent association of phospholipase C-gamma1 with c-Cbl | journal = Experimental Cell Research | volume = 277 | issue = 1 | pages = 86–94 | date = July 2002 | pmid = 12061819 | doi = 10.1006/excr.2002.5545 }}{{cite journal | vauthors = Bedrin MS, Abolafia CM, Thompson JF | title = Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells | journal = Journal of Cellular Physiology | volume = 172 | issue = 1 | pages = 126–36 | date = July 1997 | pmid = 9207933 | doi = 10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-A | s2cid = 24571987 }}
• PLSCR1,{{cite journal | vauthors = Sun J, Nanjundan M, Pike LJ, Wiedmer T, Sims PJ | title = Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor | journal = Biochemistry | volume = 41 | issue = 20 | pages = 6338–45 | date = May 2002 | pmid = 12009895 | doi = 10.1021/bi025610l }}
• PTPN1,{{cite journal | vauthors = Sarmiento M, Puius YA, Vetter SW, Keng YF, Wu L, Zhao Y, Lawrence DS, Almo SC, Zhang ZY | title = Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition | journal = Biochemistry | volume = 39 | issue = 28 | pages = 8171–9 | date = July 2000 | pmid = 10889023 | doi = 10.1021/bi000319w }}{{cite journal | vauthors = Zhang ZY, Walsh AB, Wu L, McNamara DJ, Dobrusin EM, Miller WT | title = Determinants of substrate recognition in the protein-tyrosine phosphatase, PTP1 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 10 | pages = 5386–92 | date = March 1996 | pmid = 8621392 | doi = 10.1074/jbc.271.10.5386 | doi-access = free }}
• PTPN11,{{cite journal | vauthors = Tomic S, Greiser U, Lammers R, Kharitonenkov A, Imyanitov E, Ullrich A, Böhmer FD | title = Association of SH2 domain protein tyrosine phosphatases with the epidermal growth factor receptor in human tumor cells. Phosphatidic acid activates receptor dephosphorylation by PTP1C | journal = The Journal of Biological Chemistry | volume = 270 | issue = 36 | pages = 21277–84 | date = September 1995 | pmid = 7673163 | doi = 10.1074/jbc.270.36.21277 | doi-access = free}}
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• PTPRK,{{cite journal | vauthors = Wang SE, Wu FY, Shin I, Qu S, Arteaga CL | title = Transforming growth factor {beta} (TGF-{beta})-Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function | journal = Molecular and Cellular Biology | volume = 25 | issue = 11 | pages = 4703–15 | date = June 2005 | pmid = 15899872 | pmc = 1140650 | doi = 10.1128/MCB.25.11.4703-4715.2005 }}
• SH2D3A,{{cite journal | vauthors = Lu Y, Brush J, Stewart TA | title = 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 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 10047–52 | date = April 1999 | pmid = 10187783 | doi = 10.1074/jbc.274.15.10047 | doi-access = free }}
• SH3KBP1,{{cite journal | vauthors = Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I | title = Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors | journal = Nature | volume = 416 | issue = 6877 | pages = 183–7 | date = March 2002 | pmid = 11894095 | doi = 10.1038/416183a | bibcode = 2002Natur.416..183S | s2cid = 635702 }}{{cite journal | vauthors = Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I | title = CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39666–72 | date = October 2002 | pmid = 12177062 | doi = 10.1074/jbc.M205535200 | doi-access = free }}
• SHC1,{{cite journal | vauthors = Sakaguchi K, Okabayashi Y, Kido Y, Kimura S, Matsumura Y, Inushima K, Kasuga M | title = Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth factor receptors and mediates Ras activation in intact cells | journal = Molecular Endocrinology | volume = 12 | issue = 4 | pages = 536–43 | date = April 1998 | pmid = 9544989 | doi = 10.1210/mend.12.4.0094 | doi-access = free }}
• SOS1,{{cite journal | vauthors = Qian X, Esteban L, Vass WC, Upadhyaya C, Papageorge AG, Yienger K, Ward JM, Lowy DR, Santos E | title = The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties | journal = The EMBO Journal | volume = 19 | issue = 4 | pages = 642–54 | date = February 2000 | pmid = 10675333 | pmc = 305602 | doi = 10.1093/emboj/19.4.642 }}{{cite journal | vauthors = Qian X, Vass WC, Papageorge AG, Anborgh PH, Lowy DR | title = N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains | journal = Molecular and Cellular Biology | volume = 18 | issue = 2 | pages = 771–8 | date = February 1998 | pmid = 9447973 | pmc = 108788 | doi = 10.1128/mcb.18.2.771}}
• Src,{{cite journal | vauthors = Keely SJ, Calandrella SO, Barrett KE | title = Carbachol-stimulated transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T(84) cells is mediated by intracellular Ca2+, PYK-2, and p60(src) | journal = The Journal of Biological Chemistry | volume = 275 | issue = 17 | pages = 12619–25 | date = April 2000 | pmid = 10777553 | doi = 10.1074/jbc.275.17.12619 | doi-access = free }}{{cite journal | vauthors = Sato K, Kimoto M, Kakumoto M, Horiuchi D, Iwasaki T, Tokmakov AA, Fukami Y | title = Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells | journal = Genes to Cells | volume = 5 | issue = 9 | pages = 749–64 | date = September 2000 | pmid = 10971656 | doi = 10.1046/j.1365-2443.2000.00358.x | s2cid = 26366427 | doi-access = }}
• STAT1,{{cite journal | vauthors = Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM, Platt A, Gilmer TM, Fu XY, Chin YE | title = 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 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 34 | pages = 30716–23 | date = August 2002 | pmid = 12070153 | doi = 10.1074/jbc.M202823200 | doi-access = free }}
• STAT3,{{cite journal | vauthors = Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE | title = Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells | journal = Molecular and Cellular Biology | volume = 24 | issue = 21 | pages = 9390–400 | date = November 2004 | pmid = 15485908 | pmc = 522220 | doi = 10.1128/MCB.24.21.9390-9400.2004 }}
• STAT5A,{{cite journal | vauthors = Schulze WX, Deng L, Mann M | title = Phosphotyrosine interactome of the ErbB-receptor kinase family | journal = Molecular Systems Biology | volume = 1 | issue = 1 | pages = E1–E13 | year = 2005 | pmid = 16729043 | pmc = 1681463 | doi = 10.1038/msb4100012 }}
• UBC,{{cite journal | vauthors = Sehat B, Andersson S, Girnita L, Larsson O | title = 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 | journal = Cancer Research | volume = 68 | issue = 14 | pages = 5669–77 | date = July 2008 | pmid = 18632619 | doi = 10.1158/0008-5472.CAN-07-6364 | doi-access = }} and
• WAS,{{cite journal | vauthors = She HY, Rockow S, Tang J, Nishimura R, Skolnik EY, Chen M, Margolis B, Li W | title = Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells | journal = Molecular Biology of the Cell | volume = 8 | issue = 9 | pages = 1709–21 | date = September 1997 | pmid = 9307968 | pmc = 305731 | doi = 10.1091/mbc.8.9.1709 }}
• PAR2.{{cite journal | vauthors = Jiang Y, Lim J, Wu KC, Xu W, Suen JY, Fairlie DP | title = PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR | journal = British Journal of Pharmacology | volume = (n/a) | issue = (n/a) | date = November 2020 | pages = 913–932 | pmid = 33226635 | doi = 10.1111/bph.15332|issn=0007-1188 | s2cid = 227135487 | doi-access = free }}{{Div col end}}

In fruitflies, the epidermal growth factor receptor interacts with Spitz.{{cite journal | vauthors = Shilo BZ | title = Signaling by the Drosophila epidermal growth factor receptor pathway during development | journal = Experimental Cell Research | volume = 284 | issue = 1 | pages = 140–9 | date = March 2003 | pmid = 12648473 | doi = 10.1016/S0014-4827(02)00094-0 }}

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{{refend}}

• {{MeshName|Epidermal+Growth+Factor+Receptor|3=Epidermal Growth Factor Receptor}}
• {{PDBe-KB2|P00533|Human Epidermal growth factor receptor}}

{{PDB Gallery|geneid=1956}}

{{Oncogenes}}

{{Growth factor receptors}}

{{Tyrosine kinases}}

{{Enzymes}}

{{Growth factor receptor modulators}}

{{Portal bar|Biology|border=no}}

{{DEFAULTSORT:Epidermal Growth Factor Receptor}}

Category:Tyrosine kinase receptors

Category:Oncogenes