{"entity": "publication", "iuid": "de71697736f74b5fb891aa0a05150ea3", "timestamp": "2026-08-20T21:55:38.437Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/de71697736f74b5fb891aa0a05150ea3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/de71697736f74b5fb891aa0a05150ea3"}}, "title": "The type II TGF-\u03b2 receptor phosphorylates Tyr182 in the type I receptor to activate downstream Src signaling.", "authors": [{"family": "Yakymovych", "given": "Ihor", "initials": "I", "orcid": "0000-0003-1860-5369", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/465de9e47634452fac8adf60f4b71f3e.json"}}, {"family": "Yakymovych", "given": "Mariya", "initials": "M"}, {"family": "Hamidi", "given": "Anahita", "initials": "A", "orcid": "0000-0002-5445-2446", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c9d2a9063065410385248b810cc9790f.json"}}, {"family": "Landstr\u00f6m", "given": "Mar\u00e9ne", "initials": "M", "orcid": "0000-0001-6737-7230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8cbb0a1e30bf44a2a267e6a3090acf01.json"}}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bca6678f5eb4baf853fca6ed5f9b726.json"}}], "type": "journal article", "published": "2022-11-15", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "15", "issue": "760", "pages": "eabp9521", "issn-l": "1945-0877"}, "abstract": "Transforming growth factor-\u03b2 (TGF-\u03b2) signaling has important roles during embryonic development and in tissue homeostasis. TGF-\u03b2 ligands exert cellular effects by binding to type I (T\u03b2RI) and type II (T\u03b2RII) receptors and inducing both SMAD-dependent and SMAD-independent intracellular signaling pathways, the latter of which includes the activation of the tyrosine kinase Src. We investigated the mechanism by which TGF-\u03b2 stimulation activates Src in human and mouse cells. Before TGF-\u03b2 stimulation, inactive Src was complexed with T\u03b2RII. Upon TGF-\u03b21 stimulation, T\u03b2RII associated with and phosphorylated T\u03b2RI at Tyr182. Binding of Src to T\u03b2RI involved the interaction of the Src SH2 domain with phosphorylated Tyr182 and the interaction of the Src SH3 domain with a proline-rich region in T\u03b2RI and led to the activation of Src kinase activity and Src autophosphorylation. TGF-\u03b21-induced Src activation required the kinase activities of T\u03b2RII and Src but not that of T\u03b2RI. Activated Src also phosphorylated T\u03b2RI on several tyrosine residues, which may stabilize the binding of Src to the receptor. Src activation was required for the ability of TGF-\u03b2 to induce fibronectin production and migration in human breast carcinoma cells and to induce \u03b1-smooth muscle actin and actin reorganization in mouse fibroblasts. Thus, TGF-\u03b2 induces Src activation by stimulating a direct interaction with T\u03b2RI that depends on tyrosine phosphorylation of T\u03b2RI by T\u03b2RII.", "doi": "10.1126/scisignal.abp9521", "pmid": "36378749", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:59:45.050Z", "modified": "2026-08-20T11:59:45.226Z"}