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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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
Externally publishedYes

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Serum Response Factor
Phosphorylation
Transcription
Actins
Genes
Threonine
Substitution reactions
Phosphotransferases
Chemical activation
Dimerization
Myoblasts
COS Cells
Phosphoproteins
DNA
Aspartic Acid
Alanine
Protein Kinase C
Neurons
Muscle
Muscles

ASJC Scopus subject areas

  • Biochemistry

Cite this

Iyer, D., Belaguli, N., Flück, M., Rowan, B. G., Wei, L., Weigel, N. L., ... 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

Novel phosphorylation target in the serum response factor MADS box regulates α-actin transcription. / Iyer, Dinakar; Belaguli, Narasimhaswamy; Flück, Martin; Rowan, Brian G.; Wei, Lei; Weigel, Nancy L.; Booth, Frank W.; Epstein, Henry F.; Schwartz, Robert J.; Balasubramanyam, Ashok.

In: Biochemistry, Vol. 42, No. 24, 24.06.2003, p. 7477-7486.

Research output: Contribution to journalArticle

Iyer, D, Belaguli, N, Flück, M, Rowan, BG, Wei, L, Weigel, NL, Booth, FW, Epstein, HF, Schwartz, RJ & Balasubramanyam, A 2003, 'Novel phosphorylation target in the serum response factor MADS box regulates α-actin transcription', Biochemistry, vol. 42, no. 24, pp. 7477-7486. https://doi.org/10.1021/bi030045n
Iyer, Dinakar ; Belaguli, Narasimhaswamy ; Flück, Martin ; Rowan, Brian G. ; Wei, Lei ; Weigel, Nancy L. ; Booth, Frank W. ; Epstein, Henry F. ; Schwartz, Robert J. ; Balasubramanyam, Ashok. / Novel phosphorylation target in the serum response factor MADS box regulates α-actin transcription. In: Biochemistry. 2003 ; Vol. 42, No. 24. pp. 7477-7486.
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