Termination of TGF-β Superfamily Signaling Through SMAD Dephosphorylation—A Functional Genomic View

Xia Lin^{a, c},
Yeguang Chen^d,
Anming Meng^d,
Xinhua Feng^{a, b, c
, ,}

a.
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston TX 77030, USA
b.
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston TX 77030, USA
c.
Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston TX 77030, USA
d.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China

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Corresponding author: E-mail address: xfeng@bcm.edu (Xinhua Feng)

摘要

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Abstract: The transforming growth factor-β (TGF-β) and related growth factors activate a broad range of cellular responses in metazoan organisms via autocrine, paracrine, and endocrine modes. They play key roles in the pathogenesis of many diseases especially cancer, fibrotic diseases, autoimmune diseases and cardiovascular diseases. TGF-β receptor-mediated phosphorylation of R-SMADs represents the most critical step in the TGF-β signaling pathways that triggers a cascade of intracellular events from SMAD complex assembly in the cytoplasm to transcriptional control in the nucleus. Conversely, dephosphorylation of R-SMADs is a key mechanism for terminating TGF-β signaling. Our labs have recently taken an integrated approach combining functional genomics, biochemistry and development biology to describe the isolation and functional characterization of protein phosphatase PPM1A in controlling TGF-β signaling. This article briefly reviews how dynamic phosphorylation and dephosphorylation of SMADs control or fine-tune the signaling strength and duration and ultimately the physiological consequences in TGF-β signaling.
- transforming growth factor-β (TGF-β) /
- SMADs /
- dephosphorylation

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参考文献(105)

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