Novel phosphorylation target in the serum response factor MADS box regulates α-actin transcription

Dinakar Iyer, Narasimhaswamy Belaguli, Martin Flück, Brian G. Rowan, Lei Wei, Nancy L. Weigel, Frank W. Booth, Henry F. Epstein, Robert J. Schwartz, Ashok Balasubramanyam

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Abstract

Serum response factor (SRF) is a phosphoprotein that regulates skeletal and cardiac α-actin gene transcription. Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac α-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. DMPK phosphorylated SRF in vitro in the αI coil of the DNA-binding domain in the MADS box, a highly conserved region required for DNA binding, dimerization, and co-activator interaction in COS and CV1 cells. Threonine 159 in the MADS box αI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-α. Substitution of threonine 159 with the nonphosphorylatable residue alanine markedly diminished activation of the cardiac α-actin promoter in the presence of kinase, while its substitution with aspartic acid, to introduce a negative charge and mimic phosphorylation, restored activation completely. Phosphorylation of the MADS box may constitute a novel mechanism for regulation of SRF-dependent actin gene transcription.

Original languageEnglish (US)
Pages (from-to)7477-7486
Number of pages10
JournalBiochemistry
Volume42
Issue number24
DOIs
StatePublished - Jun 24 2003

ASJC Scopus subject areas

  • Biochemistry

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    Iyer, D., Belaguli, N., Flück, M., Rowan, B. G., Wei, L., Weigel, N. L., Booth, F. W., Epstein, H. F., Schwartz, R. J., & Balasubramanyam, A. (2003). Novel phosphorylation target in the serum response factor MADS box regulates α-actin transcription. Biochemistry, 42(24), 7477-7486. https://doi.org/10.1021/bi030045n