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Updated: May 1, 2026

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic phosphatase PPM1H
Tao Shen1, Chuang Sun2, Zhengmao Zhang3
11] Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA [2] Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA [3] Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
Abstract:
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.
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