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| GADD34-PP1c recruited by Smad7 dephosphorylates TGF beta type 1 receptor |
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| Author(s): Shi WB, Sun CX, He B, Xiong WC, Shi XM, Yao DC, Cao X |
| Source: JOURNAL OF CELL BIOLOGY Volume: 164 Issue: 2 Pages: 291-300 Published: JAN 19 2004 |
| Times Cited: 66 References: 41 |
| Abstract: he cascade of phosphorylation is a pivotal event in transforming growth factor beta (TGFbeta) signaling. Reversible phosphorylation regulates fundamental aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta type I receptor; TbetaRI) functioning as a receptor kinase antagonist. We found Smac17 interacts with growth arrest and DNA damage protein, GADD34, a regulatory subunit of the protein phosphatase I (PP1) holoenzyme, which subsequently recruits catalytic subunit of PP1 (PP1c) to dephosphorylate TbetaRI. Blocking Smac17 expression by RNA interference inhibits association of GADD34-PP1c complex with TbetaRI, indicating Smad7 acts as an adaptor protein in the formation of the PP1 holoenzyme that targets TbetaRI for dephosphorylation. SARA (Smad anchor for receptor activation) enhances the recruitment PP1c to the Smad7-GADD34 complex by controlling the specific subcellular localization of PP1c. importantly, GADD34-PP1c recruited by Smad7 inhibits TGFbeta-induced cell cycle arrest and mediates TGFbeta resistance in responding to UV light irradiation. The dephosphorylation of TbetaRI mediated by Smac17 is an effective mechanism for governing negative feedback in TGFbeta signaling. |
| Document Type: Article |
| Language: English |
| Reprint Address: Cao, X (reprint author), , 1670 Univ Blvd,VH G002, Birmingham, AL 35294 USA |
Addresses:
1. Univ Alabama, Sch Med, Dept Pathol, Birmingham, AL 35294 USA
2. Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA |
| Subject Category: Cell Biology |
| IDS Number: 766HL |
| ISSN: 0021-9525 |
| DOI: 10.1083/jcb.200307151 |
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