Distinct mechanisms for the activation of the RSK kinases/MAP2 kinase/pp90rsk and pp70-S6 kinase signaling systems are indicated by inhibition of protein synthesis.
Previous studies demonstrated that addition of protein synthesis inhibitors to quiescent cells resulted in the stimulation of S6 kinase activity. The present characterization of several growth factor- and oncogene-regulated protein-serine/threonine kinases demonstrated that pp70-S6 protein kinase and not pp90rsk, RSK kinase, or MAP2 kinase activities were rapidly stimulated. Dose-response experiments revealed a close correlation between the extent of protein synthesis inhibition and the level of activation of pp70-S6 kinase activity. Analysis of S6 phosphorylation suggests that activation of pp90rsk S6 phosphotransferase activity, whose Xenopus homologues appear to be responsible for S6 phosphorylation during oocyte maturation, may participate in, but is not essential for, the increase in S6 phosphorylation observed in growth-stimulated somatic animal cells. These studies provide additional evidence for the existence of two distinct, independently regulated protein phosphorylation cascades activated in the early G1 phase of the cell cycle.
Blenis
J
J
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
Chung
J
J
Erikson
E
E
Alcorta
D A
DA
Erikson
R L
RL
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002453:Cell Cycle / Q000502:physiology; D002461:Cell Line, Transformed; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011691:Puromycin / Q000494:pharmacology; D019893:Ribosomal Protein S6 Kinases; D012269:Ribosomal Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D012269:Ribosomal Proteins; D014638:Vanadates; D011691:Puromycin; D003513:Cycloheximide; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases