Stimulation of ribosomal protein S6 kinase activity by pp60v-src or by serum: dissociation from phorbol ester-stimulated activity.
Ribosomal protein S6 kinase activity was measured in lysates prepared from serum-deprived chicken embryo fibroblasts (CEF) treated for various times with phorbol 12-myristate 13-acetate (PMA). Maximal activity was observed within 15 min, and it declined to the initial level by 4 hr. Incubation of these cells with PMA 4-60 hr after the initial treatment did not result in an additional increase in S6 protein kinase activity. These results are consistent with down-regulation of the PMA receptor, protein kinase C, and the dependence of PMA-stimulated S6 kinase activity on this enzyme. Long-term pretreatment of CEF with PMA only partially attenuated the stimulation of the S6 protein kinase activity by serum or by expression of the Rous sarcoma virus transforming gene product, pp60v-src. A similar protein kinase activity also was stimulated in cells treated with cycloheximide or sodium vanadate. Pretreatment with PMA had little effect on this response. These data indicate that it is likely that there are at least two mechanisms through which S6 kinase activity can be regulated, one of which apparently utilizes protein kinase C whereas the other(s) does not. Additional experiments show PMA-stimulated glucose transport was not attenuated by long-term incubation with phorbol ester, suggesting that another mechanism, which is not dependent on the presence of protein kinase C, maintains this response after the proposed down-regulation of the PMA receptor.
Blenis
J
J
Erikson
R L
RL
D000818:Animals; D001790:Blood Physiological Phenomena; D002642:Chick Embryo; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src); D010704:Phorbols / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D012191:Retroviridae Proteins / Q000378:metabolism*; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology
D010704:Phorbols; D012191:Retroviridae Proteins; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D014639:Vanadium; D014638:Vanadates; D003513:Cycloheximide; D015688:Oncogene Protein pp60(v-src); D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol