Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic phosphatase PPMIH  

作　　者：Tao Shen Chuang Sun Zhengmao Zhang Ningyi Xu Xueyan Duan Xin-Hua Feng Xia Lin 

机构地区：[1]Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China [2]Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA [3]Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA [4]Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA [5]Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA

出　　处：《Cell Research》2014年第6期727-741,共15页细胞研究（英文版）

摘　　要：Bone morphogenetic proteins （BMPs） belong to the TGF-β superfamily of structurally related signaling pro teins that regulate a wide array of cellular functions. The key step in BMP signal transduction is the BMP receptormediated phosphorylation of transcription factors Smadl, 5, and 8 （collectively Smadl/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 Smadl/5/8-specific phosphatase. PPM1H directly interacts with Smadl/5/8 through its Smad-binding domain, and dephosphorylates phospho-Smadl/5/8 （P-Smadl/5/8） in the cytoplasm. Ectopic expression of PPM1H attenuates BMP signaling, whereas loss of PPM1H activity or expres- sion 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-Smadl/5/8 proteins.

关 键 词：PHOSPHORYLATION protein phosphatases signal transduction TGF-β 

分 类 号：Q959.3[生物学—动物学] Q26