Volume 24, No 6, Jun 2014
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 24 Issue 6, June 2014: 727-741
ORIGINAL ARTICLES
Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic phosphatase PPM1H
Tao Shen2,3,4, Chuang Sun2,5, Zhengmao Zhang2, Ningyi Xu1, Xueyan Duan3, Xin-Hua Feng1,2,3,5 and Xia Lin2
1Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
2Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
3Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
4Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA
5Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
Correspondence: Xin-Hua Feng,Xia Lin(xfeng@bcm.edu;xialin@bcm.edu)
Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily of structurally related signaling proteins that regulate a wide array of cellular functions. The key step in BMP signal transduction is the BMP receptor-mediated phosphorylation of transcription factors Smad1, 5, and 8 (collectively Smad1/5/8), which leads to the subsequent activation of BMP-induced gene transcription in the nucleus. In this study, we describe the identification and characterization of PPM1H as a novel cytoplasm-localized Smad1/5/8-specific phosphatase. PPM1H directly interacts with Smad1/5/8 through its Smad-binding domain, and dephosphorylates phospho-Smad1/5/8 (P-Smad1/5/8) in the cytoplasm. Ectopic expression of PPM1H attenuates BMP signaling, whereas loss of PPM1H activity or expression greatly enhances BMP-dependent gene regulation and mesenchymal differentiation. In conclusion, this study suggests that PPM1H acts as a gatekeeper to prevent excessive BMP signaling through dephosphorylation and subsequent nuclear exclusion of P-Smad1/5/8 proteins.
doi:10.1038/cr.2014.48
FULL TEXT | PDF
Browse 2024
