{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:45:52Z","timestamp":1787946352684,"version":"build-2784847793"},"reference-count":79,"publisher":"The Royal Society","issue":"1957","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The seminal discovery that the epidermal growth factor receptor (EGFR) possesses intrinsic EGF-stimulated tyrosine kinase activity that serves as a mitogenic signalling mechanism was dependent on two separate lines of research that intersected in the late 1970s and early 1980s, namely studies of retroviral transforming proteins and the identification of growth factor receptor proteins. This historical review outlines the events that ultimately led to the intersection of these two strands of research, resulting from the twin discoveries that many growth factor receptors, including EGFR, are ligand-activated receptor tyrosine kinases (RTKs), and that many retroviral transforming proteins are dysregulated tyrosine kinases that usurp RTK signalling pathways to drive continuous cell proliferation. A French translation of this abstract is available in the supplementary material.<\/jats:p>\n                  <jats:p>This article is part of the discussion meeting issue \u2018Epidermal growth factor receptor after 40 years\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2024.0495","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:08:37Z","timestamp":1787814517000},"source":"Crossref","is-referenced-by-count":1,"title":["The epidermal growth factor receptor\u2014the prototypic RTK\u2014turns 40"],"prefix":"10.1098","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-6993","authenticated-orcid":false,"given":"Tony","family":"Hunter","sequence":"first","affiliation":[{"name":"Salk Institute for Biological Studies , La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"2026082703083272500_RSTB20240495C1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/307521a0","article-title":"Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences","volume":"307","author":"Downward","year":"1984","journal-title":"Nature"},{"key":"2026082703083272500_RSTB20240495C2","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/309418a0","article-title":"Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells","volume":"309","author":"Ullrich","year":"1984","journal-title":"Nature"},{"key":"2026082703083272500_RSTB20240495C3","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/309806a0","article-title":"Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells","volume":"309","author":"Xu","year":"1984","journal-title":"Nature"},{"key":"2026082703083272500_RSTB20240495C4","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1126\/science.6326261","article-title":"Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells","volume":"224","author":"Lin","year":"1984","journal-title":"Science"},{"key":"2026082703083272500_RSTB20240495C5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0092-8674(83)90209-X","article-title":"The erbB gene of avian erythroblastosis virus is a member of the srcgene family","volume":"35","author":"Yamamoto","year":"1983","journal-title":"Cell"},{"key":"2026082703083272500_RSTB20240495C6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/276409a0","article-title":"Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro","volume":"276","author":"Carpenter","year":"1978","journal-title":"Nature"},{"key":"2026082703083272500_RSTB20240495C7","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/0092-8674(79)90205-8","article-title":"An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates","volume":"18","author":"Eckhart","year":"1979","journal-title":"Cell"},{"key":"2026082703083272500_RSTB20240495C8","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0092-8674(80)90327-X","article-title":"Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus","volume":"20","author":"Sefton","year":"1980","journal-title":"Cell"},{"key":"2026082703083272500_RSTB20240495C9","doi-asserted-by":"crossref","first-page":"8363","DOI":"10.1016\/S0021-9258(18)43497-7","article-title":"Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes","volume":"255","author":"Ushiro","year":"1980","journal-title":"J. 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