Serum Response Factor Mads Box Serine-162 Phosphorylation Switches Proliferation and Myogenic Gene Programs.
From: Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Mar 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 12
- Pages: 4516-21
- Medium: Print
- Language: English
- Citation (JAMA): Iyer Dinakar, Chang David, Marx Joe, et al. Serum Response Factor Mads Box Serine-162 Phosphorylation Switches Proliferation and Myogenic Gene Programs.. Proc. Natl. Acad. Sci. U.S.A. Mar 2006;103:4516-21
Abstract
Phosphorylation of a cluster of amino acids in the serum response factor (SRF) “MADS box” alphaI coil DNA binding domain regulated the transcription of genes associated with proliferation or terminal muscle differentiation. Mimicking phosphorylation of serine-162, a target of protein kinase C-alpha, with an aspartic acid substitution (SRF-S162D) completely inhibited SRF-DNA binding and blocked alpha-actin gene transcription even in the presence of potent myogenic cofactors, while preserving c-fos promoter activity because of stabilization of the ternary complex via Elk-1. Introduction of SRF-S162D into SRF null ES cells permitted transcription of the c-fos gene but was unable to rescue expression of myogenic contractile genes. Transition of proliferating C2C12 myoblasts to postfusion myocytes after serum withdrawal was associated with a progressive decline in SRF-S162 phosphorylation and an increase in alpha-actin gene expression. Hence, the phosphorylation status of serine-162 in the alphaI coil may constitute a novel switch that directs target gene expression into proliferation or differentiation programs.
Mesh Headings (Keywords): Actins, Amino Acid Sequence, Amino Acid Substitution, Animals, Aspartic Acid, Cell Differentiation, Cell Proliferation, Cells, Cultured, Genes, fos, Mice, Molecular Sequence Data, Muscle Contraction, Muscle Development, Muscle, Smooth, Myoblasts, Skeletal, Promoter Regions (Genetics), Protein Conformation, Protein Kinase C-alpha, Serine, Serum Response Factor, Trans-Activation (Genetics), ets-Domain Protein Elk-1
Check for Full Text / PubMed Unique Identifier (PMID): 16537394
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