C-terminal phosphorylation of the serum-response factor.
The serum-response factor (SRF) is essential for the induction and repression of the protooncogene c-fos. Phosphorylation of SRF has been implicated to be involved in these processes and five phosphorylation sites have already been mapped within the N-terminal region. Here we show that in vivo additional phosphorylation of SRF does occur. This modification is located primarily within amino acids 206-289, which probably contain more than one phosphorylation site. Microsequencing allowed the identification of one phosphorylation site at Ser253, which is a potential target of casein kinase II. Mutational analysis revealed that, in contrast to N-terminal phosphorylation, Ser253 phosphorylation does not affect DNA-binding properties. In addition, phosphorylation at Ser253 does not seem to change transactivation activity of SRF but rather influences its contribution to transcriptional repression. Thus, C-terminal phosphorylation of SRF may modulate c-fos basal repression.
Institute for Molecular Biology, Hannover Medical School, Germany.
R
R
Janknecht
W H
WH
Ernst
T
T
Houthaeve
A
A
Nordheim
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D004247:DNA