Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs

Dinakar Iyer, David Chang, Joe Marx, Lei Wei, Eric M. Olson, Michael S. Parmaceki, Ashok Balasubramanyam, Robert J. Schwartz

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Phosphorylation of a cluster of amino acids in the serum response factor (SRF) "MADS box" αI 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-α, with an aspartic acid substitution (SRF-S162D) completely inhibited SRF-DNA binding and blocked α-act in 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 α-actin gene expression. Hence, the phosphorylation status of serine-162 in the αI coil may constitute a novel switch that directs target gene expression into proliferation or differentiation programs.

Original languageEnglish (US)
Pages (from-to)4516-4521
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number12
DOIs
StatePublished - Mar 21 2006

Fingerprint

Serum Response Factor
Serine
Phosphorylation
Genes
fos Genes
Gene Expression
Null Lymphocytes
Myoblasts
DNA
Aspartic Acid
Muscle Cells
Protein Kinase C
Actins
Amino Acids
Muscles
Serum

Keywords

  • α-actin
  • c-fos
  • Differentiation
  • PKC

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs. / Iyer, Dinakar; Chang, David; Marx, Joe; Wei, Lei; Olson, Eric M.; Parmaceki, Michael S.; Balasubramanyam, Ashok; Schwartz, Robert J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 12, 21.03.2006, p. 4516-4521.

Research output: Contribution to journalArticle

Iyer, Dinakar ; Chang, David ; Marx, Joe ; Wei, Lei ; Olson, Eric M. ; Parmaceki, Michael S. ; Balasubramanyam, Ashok ; Schwartz, Robert J. / Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 12. pp. 4516-4521.
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