[Frontiers in Bioscience E2, 857-860, June 1, 2010]

Smad anchor for receptor activation (SARA) in TGF-beta signaling

Wen-bin Tang1, Guang-hui Ling1, Lin Sun1, 2, Fu-You Liu1

1Kidney institute, Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha, China, 2Department of Pathology & Medicine, Northwestern University, Chicago, Illinois, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. SARA modulate TGF-beta signaling
3.1. The subcellular localization of SARA and TGF-beta signaling
3.2. SARA regulates Smad2 and Smad3 activation
3.3. SARA and the negative regulation of TGF-beta signaling
4. SARA in TGF-beta associated EMT and fibrosis
5. Summary and perspective
6. Acknowledgement
7. Reference

1. ABSTRACT

Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor. SARA plays an essential role in TGF-beta-induced Smad2 activation and it can modulate TGF-beta signaling through verify the balances of Smad2 and Smad3. SARA also functions as an anchor for catalytic subunit of protein phosphatase 1 (PP1c) and maybe involved in the dephosphorylation of TGF-beta type I receptor (TbetaR-I) mediated by Smad7. The expression of SARA changes as the development of epithelial to mesenchymal transition (EMT) and fibrosis and it plays a critical role in the maintenance of epithelial cell phenotype. Modulation of SARA may provide a new therapeutic approach to TGF-beta-mediated EMT and fibrosis.