Differential responses of the phosphorylation of ribosomal protein S6 to nerve growth factor and epidermal growth factor in PC12 cells.
Previous studies from this laboratory have shown that the phosphorylation of the S6 protein of the ribosomes is catalyzed by at least two different and separable kinase activities in PC12 cells. One of these activities is increased by treatment of the cells with nerve growth factor, the other by treatment of the cells with epidermal growth factor. The present work shows that these two factors stimulate the phosphorylation of S6 with quite different kinetics, and that both the number of phosphates incorporated into S6 and the phosphopeptide pattern of S6 are different in cells treated with nerve growth factor than in cells treated with epidermal growth factor. The characteristics of the nerve growth factor-sensitive S6 kinase and of the epidermal growth factor-sensitive kinase were also clearly different. Substrate specificity and inhibitor studies indicated that neither was identical to cyclic AMP-dependent kinase, kinase C, or the calcium/calmodulin-dependent kinases. However, two major phosphopeptides produced by S6 phosphorylation in nerve growth factor-treated cells were also seen on phosphorylation of S6 by cyclic AMP-dependent kinase in vitro. In addition, when rat liver 40S ribosomal subunits were pretreated with cyclic AMP-dependent kinase in vitro, the action of the nerve growth factor-sensitive S6 kinase was increased about twofold.
Mutoh
T
T
Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Rudkin
B B
BB
Guroff
G
G
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D016716:PC12 Cells / Q000378:metabolism*; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000737:chemistry; D010766:Phosphorylation; D010770:Phosphotransferases / Q000302:isolation & purification; D011494:Protein Kinases / Q000494:pharmacology; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000378:metabolism*
D000596:Amino Acids; D009414:Nerve Growth Factors; D010748:Phosphopeptides; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D004815:Epidermal Growth Factor; D010770:Phosphotransferases; D011494:Protein Kinases