Nerve Growth Factor‐Induced Transient Increase in the Phosphorylation of Ribosomal Protein S6 Mediated Through a Mechanism Independent of Cyclic AMP‐Dependent Protein Kinase and Protein Kinase C

Seiichi Hashimoto, Akihiko Hagino

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Abstract: Treatment of PC12h cells with nerve growth factor (NGF) induced a transient increase in the phosphorylation of a 35,000‐dalton protein. This transient increase was observed also when extracts of NGF‐treated cells were incubated with [γ‐32P]ATP. In the intact‐cell phosphorylation system, treatment with N,2′‐dibutyryladenosine 3′,5′‐cyclic monophosphate (dBcAMP) or 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) also induced a transient increase in the phosphorylation of the 35,000‐dalton protein, but the effect was less than that of NGF. An effect comparable to that of NGF was obtained by the combination of dBcAMP and TPA. Pretreatment of PC12h cells with dBcAMP plus TPA for 3 days, which deprived the cells of their ability to respond to a re‐challenge with dBcAMP, TPA, or dBcAMP plus TPA by increasing the rate of 35,000‐dalton protein phosphorylation, caused only a slight attenuation of the NGF effect, directly indicating a minimal role of cyclic AMP (cAMP)‐dependent protein kinase and protein kinase C in the mechanism of the NGF action. Pretreatment of the cells with K‐252a, a protein kinase inhibitor, at a concentration of 300 μM almost completely blocked the action of NGF, but scarcely affected the action of dBcAMP, TPA, or dBcAMP plus TPA in intact‐cell phosphorylation experiments. This NGF‐sensitive 35,000‐dalton protein was a ribosomal protein and identified as ribosomal protein S6. The results lead us to conclude that NGF activates some NGF‐sensitive component(s), probably some specific protein kinase(s) other than cAMP‐dependent protein kinase or protein kinase C., which is suppressed by K‐252a and directly or indirectly activates a 35,000‐dalton protein kinase(s) [S6 kinase(s)] to increase the rate of phosphorylation of the 35,000‐dalton ribosomal protein (S6).

Original languageEnglish
Pages (from-to)970-980
Number of pages11
JournalJournal of Neurochemistry
Volume55
Issue number3
DOIs
Publication statusPublished - 1990 Sep
Externally publishedYes

Keywords

  • 12‐O‐Tetradecanoylphorbol 13‐acetate
  • Dibutyryl cyclic AMP
  • Nerve growth factor
  • PC12h cells
  • Protein phosphorylation
  • S6

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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