{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T03:04:43Z","timestamp":1773111883468,"version":"3.50.1"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,1,19]]},"abstract":"<jats:p>The cascade of phosphorylation is a pivotal event in transforming growth factor \u03b2 (TGF\u03b2) signaling. Reversible phosphorylation regulates fundamental aspects of cell activity. TGF\u03b2-induced Smad7 binds to type I receptor (TGF\u03b2 type I receptor; T\u03b2RI) functioning as a receptor kinase antagonist. We found Smad7 interacts with growth arrest and DNA damage protein, GADD34, a regulatory subunit of the protein phosphatase 1 (PP1) holoenzyme, which subsequently recruits catalytic subunit of PP1 (PP1c) to dephosphorylate T\u03b2RI. Blocking Smad7 expression by RNA interference inhibits association of GADD34\u2013PP1c complex with T\u03b2RI, indicating Smad7 acts as an adaptor protein in the formation of the PP1 holoenzyme that targets T\u03b2RI for dephosphorylation. SARA (Smad anchor for receptor activation) enhances the recruitment PP1c to the Smad7\u2013GADD34 complex by controlling the specific subcellular localization of PP1c. Importantly, GADD34\u2013PP1c recruited by Smad7 inhibits TGF\u03b2-induced cell cycle arrest and mediates TGF\u03b2 resistance in responding to UV light irradiation. The dephosphorylation of T\u03b2RI mediated by Smad7 is an effective mechanism for governing negative feedback in TGF\u03b2 signaling.<\/jats:p>","DOI":"10.1083\/jcb.200307151","type":"journal-article","created":{"date-parts":[[2004,1,13]],"date-time":"2004-01-13T01:24:08Z","timestamp":1073957048000},"page":"291-300","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":217,"title":["GADD34\u2013PP1c recruited by Smad7 dephosphorylates TGF\u03b2 type I receptor"],"prefix":"10.1083","volume":"164","author":[{"given":"Weibin","family":"Shi","sequence":"first","affiliation":[{"name":"1Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanxi","family":"Sun","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wencheng","family":"Xiong","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingming","family":"Shi","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dachun","family":"Yao","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Cao","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2004,1,12]]},"reference":[{"key":"2023072214525155400_BIB1","doi-asserted-by":"crossref","first-page":"27678","DOI":"10.1074\/jbc.272.44.27678","volume":"272","year":"1997","journal-title":"J. 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