Signal transduction within the nucleus by mitogen-activated protein kinase.
The nucleus is an important target of signal transduction by growth factor receptors that stimulate mitogen-activated protein (MAP) kinases. We tested the hypothesis that MAP kinases have a signaling role within the nucleus by examining the effect of the expression of a human MAP kinase isoform (p41mapk) in tissue culture cells. The expressed p41mapk was found to be localized in both the cytoplasmic and nuclear compartments of the cells. Significantly, the expression of p41mapk caused an increase in the phosphorylation of a nuclear substrate: Ser62 of c-Myc. Phosphorylation at Ser62 stimulated the activity of the NH2-terminal transactivation domain of c-Myc. Thus, p41mapk causes the phosphorylation and regulation of a physiologically significant nuclear target of signal transduction. These data establish that at least one MAP kinase isoform has a nuclear role during signal transduction.
Seth
A
A
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605.
Gonzalez
F A
FA
Gupta
S
S
Raden
D L
DL
Davis
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D010748:Phosphopeptides / Q000302:isolation & purification; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012694:Serine; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection
D007527:Isoenzymes; D010455:Peptides; D010748:Phosphopeptides; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D012694:Serine; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases