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Smad7 and protein phosphatase 1α are critical determinants in the duration of TGF-β/ALK1 signaling in endothelial cells

Authors
Publisher
BioMed Central
Publication Date
Source
PMC
Keywords
  • Research Article
Disciplines
  • Biology
  • Chemistry
  • Medicine

Abstract

1471-2121-7-16.fm ral ss BioMed CentBMC Cell Biology Open AcceResearch article Smad7 and protein phosphatase 1α are critical determinants in the duration of TGF-β/ALK1 signaling in endothelial cells Gudrun Valdimarsdottir1, Marie-José Goumans2, Fumiko Itoh3, Susumu Itoh3, Carl-Henrik Heldin3 and Peter ten Dijke*5,4 Address: 1Dept. of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland, 2Heart Lung Center, Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands, 3Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305–8575, Japan, 44Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, S-751 24, Uppsala, Sweden and 5Molecular Cell Biology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands Email: Gudrun Valdimarsdottir - [email protected]; Marie-José Goumans - [email protected]; Fumiko Itoh - [email protected]; Susumu Itoh - [email protected]; Carl-Henrik Heldin - [email protected]; Peter ten Dijke* - [email protected] * Corresponding author Abstract Background: In endothelial cells (EC), transforming growth factor-β (TGF-β) can bind to and transduce signals through ALK1 and ALK5. The TGF-β/ALK5 and TGF-β/ALK1 pathways have opposite effects on EC behaviour. Besides differential receptor binding, the duration of TGF-β signaling is an important specificity determinant for signaling responses. TGF-β/ALK1-induced Smad1/5 phosphorylation in ECs occurs transiently. Results: The temporal activation of TGF-β-induced Smad1/5 phosphorylation in ECs was found to be affected by de novo protein synthesis, and ALK1 and Smad5 expression levels determined signal strength of TGF-β/ALK1 signaling pathway. Smad7 and protein phosphatase 1α (PP1α) mRNA expression levels were found to be specifically upregulated by TGF-β/ALK1. Ectopic ex

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