期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 25, 页码 18327-18338出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M700636200
关键词
-
资金
- NCI NIH HHS [R01 CA095527, CA095527] Funding Source: Medline
The primary intracellular mediators of TGF-beta signaling are the Smad proteins. Phosphorylation of R-Smad at the C-terminal SSXS motif by the activated TGF-beta type I receptor kinase triggers a conformation change in R-Smad and facilitates complex formation between R- Smad and Smad4, which shuttle into the nucleus where they interact with DNA and other transcription factors to regulate gene expression. In an attempt to identify proteins interacting with activated Smad signaling complex, we discovered that Mps1, a protein kinase that plays important roles in normal mitotic progression and mitotic checkpoint signaling, co-purifies with this complex. We demonstrated that Smad2 and Smad3 but not Smad4 are substrates of Mps1 in vitro and in vivo. Mps1 phosphorylates Smad2 and Smad3 at the SSXS motif in their C-terminal regions in vitro and in vivo. Disruption of microtubule networks by nocodazole activates Mps1 and promotes TGF-beta-independent activation of Smad signaling. We found that Mps1 is involved in turning on Smad signaling by phosphorylating R-Smads. Our results reveal a novel functional link between Mps1 and Smads in a non-canonical Smad signaling pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据