{"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":1787946352468,"version":"build-2784847793"},"reference-count":41,"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\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","award":["GM142164"],"award-info":[{"award-number":["GM142164"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"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 epidermal growth factor (EGF) receptor is a canonical receptor tyrosine kinase with an extracellular ligand-binding domain, a single-pass transmembrane domain and an intracellular kinase domain. Binding of an agonist ligand leads to the dimerization of the receptor and activation of its tyrosine kinase activity. This results in autophosphorylation of the receptor on its C-terminal tail and the activation of downstream signalling pathways that mediate the intracellular effects of the agonist. The receptor binds seven different ligands. Structural studies have shown that the ligands bind to the same site on the EGF receptor and induce the formation of receptor dimers. Nonetheless, different agonists can elicit markedly different biological effects in the same cell, such as proliferation versus differentiation. This phenomenon is known as ligand bias, since the ligand biases the system to progress down one biological pathway as opposed to another. This review summarizes recent studies that have provided insight into the molecular mechanism of ligand bias in the EGF receptor system. 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\u2018.<\/jats:p>","DOI":"10.1098\/rstb.2025.0050","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:10:06Z","timestamp":1787814606000},"source":"Crossref","is-referenced-by-count":1,"title":["Ligand bias in the EGF receptor system"],"prefix":"10.1098","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6708-5008","authenticated-orcid":false,"given":"Linda J.","family":"Pike","sequence":"first","affiliation":[{"name":"School of Medicine, Washington University in Saint Louis , Saint Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"2026082703095651800_RSTB20250050C1","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":"2026082703095651800_RSTB20250050C2","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0092-8674(02)00940-6","article-title":"Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor a","volume":"110","author":"Garrett","year":"2002","journal-title":"Cell"},{"key":"2026082703095651800_RSTB20250050C3","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S0092-8674(02)00963-7","article-title":"Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains","volume":"110","author":"Ogiso","year":"2002","journal-title":"Cell"},{"key":"2026082703095651800_RSTB20250050C4","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1021\/bi00379a034","article-title":"Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation","volume":"26","author":"Yarden","year":"1987","journal-title":"Biochemistry"},{"key":"2026082703095651800_RSTB20250050C5","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1021\/bi00379a035","article-title":"Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor","volume":"26","author":"Yarden","year":"1987","journal-title":"Biochemistry"},{"key":"2026082703095651800_RSTB20250050C6","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nrm1962","article-title":"EGF\u2013ErbB signalling: towards the systems level","volume":"7","author":"Citri","year":"2006","journal-title":"Nat. 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