Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 12, Pages 4516-4521Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0505338103
Keywords
PKC; differentiation; alpha-actin; c-fos
Categories
Funding
- NHLBI NIH HHS [P01 HL049953, R01 HL072897, R01 HL 73696, R01 HL056915, HL 079628, R01 HL 56915, P01 HL 49953, R01 HL073696, R01 HL072897-02, P01 HL 75380, R01 HL079628] Funding Source: Medline
- NIDDK NIH HHS [R01 DK 59537, R01 DK059537] Funding Source: Medline
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Phosphorylation of a cluster of amino acids in the serum response factor (SRIF) MADS box alpha l 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-a, 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 al coil may constitute a novel switch that directs target gene expression into proliferation or differentiation programs.
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