{"entity": "researcher", "timestamp": "2026-10-01T12:33:13.706Z", "family": "Song", "given": "Jie", "initials": "J", "orcid": "0000-0002-4955-9118", "affiliations": ["Unit of Pathology, Department of Medical Biosciences, Ume\u00e5 University, Ume\u00e5 SE 901 85, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdffbb7fd85e498b9cdc11d99be89dd9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdffbb7fd85e498b9cdc11d99be89dd9"}}, "publications": [{"entity": "publication", "iuid": "c9a9c522a26e4e15afb57d85a1d5ea75", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c9a9c522a26e4e15afb57d85a1d5ea75.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c9a9c522a26e4e15afb57d85a1d5ea75"}}, "title": "TGF-\u03b2 promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85\u03b1.", "authors": [{"family": "Hamidi", "given": "Anahita", "initials": "A", "orcid": "0000-0002-5445-2446", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c9d2a9063065410385248b810cc9790f.json"}}, {"family": "Song", "given": "Jie", "initials": "J", "orcid": "0000-0002-4955-9118", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdffbb7fd85e498b9cdc11d99be89dd9.json"}}, {"family": "Thakur", "given": "Noopur", "initials": "N"}, {"family": "Itoh", "given": "Susumu", "initials": "S", "orcid": "0000-0002-7967-0730", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/573c5d7ad0214195a9236b04d016e1b7.json"}}, {"family": "Marcusson", "given": "Anders", "initials": "A"}, {"family": "Bergh", "given": "Anders", "initials": "A", "orcid": "0000-0001-5163-5821", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/860599ecc7944738ac03ba181867ba47.json"}}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bca6678f5eb4baf853fca6ed5f9b726.json"}}, {"family": "Landstr\u00f6m", "given": "Mar\u00e9ne", "initials": "M", "orcid": "0000-0001-6737-7230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8cbb0a1e30bf44a2a267e6a3090acf01.json"}}], "type": "journal article", "published": "2017-07-04", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "10", "issue": "486", "issn-l": "1945-0877"}, "abstract": "Transforming growth factor-\u03b2 (TGF-\u03b2) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues and tumors. The multifunctional cellular responses evoked by TGF-\u03b2 are mediated by the canonical SMAD pathway and by noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways and the phosphatidylinositol 3'-kinase (PI3K)-protein kinase B (AKT) pathway. We found that TGF-\u03b2 activated PI3K in a manner dependent on the activity of the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6). TRAF6 polyubiquitylated the PI3K regulatory subunit p85\u03b1 and promoted the formation of a complex between the TGF-\u03b2 type I receptor (T\u03b2RI) and p85\u03b1, which led to the activation of PI3K and AKT. Lys63-linked polyubiquitylation of p85\u03b1 on Lys513 and Lys519 in the iSH2 (inter-Src homology 2) domain was required for TGF-\u03b2-induced activation of PI3K-AKT signaling and cell motility in prostate cancer cells and activated macrophages. Unlike the activation of SMAD pathways, the TRAF6-mediated activation of PI3K and AKT was not dependent on the kinase activity of T\u03b2RI. In situ proximity ligation assays revealed that polyubiquitylation of p85\u03b1 was evident in aggressive prostate cancer tissues. Thus, our data reveal a molecular mechanism by which TGF-\u03b2 activates the PI3K-AKT pathway to drive cell migration.", "doi": "10.1126/scisignal.aal4186", "pmid": "28676490", "labels": [], "xrefs": [{"db": "pii", "key": "10/486/eaal4186"}], "notes": [], "created": "2018-12-05T11:04:39.791Z", "modified": "2026-10-01T08:22:59.959Z"}]}