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Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic phosphatase PPM1H.


ABSTRACT: Bone morphogenetic proteins (BMPs) belong to the TGF-? 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.

SUBMITTER: Shen T 

PROVIDER: S-EPMC4042171 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic phosphatase PPM1H.

Shen Tao T   Sun Chuang C   Zhang Zhengmao Z   Xu Ningyi N   Duan Xueyan X   Feng Xin-Hua XH   Lin Xia X  

Cell research 20140415 6


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-  ...[more]

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