Evidence for two catalytically active kinase domains in pp90rsk.
Mitogen-activated protein kinase and one of its targets, pp90rsk (ribosomal S6 kinase [RSK]), represent two serine/threonine kinases in the Ras-activated signalling cascade that are capable of directly regulating gene expression. pp90rsk has been shown to have two highly conserved and distinct catalytic domains. However, whether both domains are active and which domain is responsible for its various identified phosphotransferase activities have not been determined. Here we demonstrate that the N-terminal domain is responsible for its phosphotransferase activity towards a variety of substrates which contain an RXXS motif at the site of in vitro phosphorylation, including serum response factor, c-Fos, Nur77, and the 40S ribosomal protein S6. We also provide evidence that the C-terminal domain is catalytically active and can be further activated by mitogen-activated protein kinase phosphorylation.
Fisher
T L
TL
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Blenis
J
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D017421:Sequence Analysis
D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases