Transcriptional regulation of a rat hepatoma gene by insulin and protein kinase-c

Academic Article


  • Both insulin and phorbol esters rapidly stimulated the cytoplasmic accumulation of a specific mRNA (designated p33) in a time- and dose-dependent manner in serumdeprived rat H4 hepatoma cells. When cells were pretreated with phorbol esters to produce a deficiency in protein kinase-C, the ability of further phorbol ester addition to stimulate p33 mRNA accumulation was abolished. However, after pretreatment of H4 cells with phorbol esters, insulin still induced cellular p33 mRNA concentrations, but to a lesser degree. The primary effect of phorbol esters was to increase transcription of the p33 gene, and this was abolished after pretreatment with phorbol esters. In previous work, insulin was shown to stimulate p33 gene transcription, but this effect was insufficient to account for the level of insulin-induced p33 mRNA production. The transcriptional effect of insulin was further reduced by phorbol ester pretreatment. Insulin must, therefore, regulate p33 gene expression by at least two pathways, at least one of which may be modulated by protein kinase-C. © 1988 by The Endocrine Society.
  • Published In

  • Endocrinology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Weinstock RS; Messina JL
  • Start Page

  • 366
  • End Page

  • 372
  • Volume

  • 123
  • Issue

  • 1