Fos is phosphorylated by p34cdc2, cAMP-dependent protein kinase and protein kinase C at multiple sites clustered within regulatory regions.
The proto-oncogene c-fos encodes a nuclear protein (Fos) that functions in transcriptional regulation in response to extracellular signals. Fos is extensively modified in the nucleus by serine and threonine phosphorylation. It has been suggested that phosphorylation may play an important role in regulating Fos function in normal and transformed cells. As a first step in addressing this issue, we have used purified Fos as a substrate for several serine-threonine protein kinases, including cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and p34cdc2. Each of these kinases phosphorylated Fos at several unique sites. These sites were located within two regions that were previously shown to reduce the transcriptional activity of Fos in vitro. Several of the sites modified in vitro were also shown to be phosphorylated in serum-stimulated fibroblasts. These findings demonstrate that Fos is a target for several protein kinases involved in signal transduction and suggest that phosphorylation could regulate the transcriptional properties of Fos.
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Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
Marshak
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Curran
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D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002460:Cell Line; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013379:Substrate Specificity; D014158:Transcription, Genetic
D010748:Phosphopeptides; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D011494:Protein Kinases; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase