Endogenous protein kinase inhibitor γ terminates immediate-early gene expression induced by cAMP-dependent protein kinase (PKA) signaling: Termination depends on PKA inactivation rather than PKA export from the nucleus

Xin Chen, Jia Chun Dai, Stephanie A. Orellana, Edward M. Greenfield

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Expression of many genes induced by cAMP-dependent protein kinase (PKA) signaling is rapidly terminated. Although many mechanisms contribute to regulation of PKA signaling, members of the endogenous protein kinase inhibitor (PKI) family may be particularly important for terminating nuclear PKA activity and gene expression. Here we used both siRNA and antisense knockdown strategies to examine PKA signaling activated by parathyroid hormone or the β-adrenergic agonist, isoproterenol. We found that endogenous PKIγ is required for efficient termination of nuclear PKA activity, transcription factor phosphorylation, and immediate-early genes. Moreover, PKIγ is required for export of PKA catalytic subunits from the nucleus back to the cytoplasm following activation of PKA signaling because this is also inhibited by PKIγ knockdown. Leptomycin B blocks PKA nuclear export but has little or no effect on nuclear PKA activity or immediate-early gene expression. Thus, inactivation of PKA activity in the nucleus is sufficient to terminate signaling, and nuclear export is not required. These results were the first in any cell type showing that endogenous levels of PKI regulate PKA signaling.

Original languageEnglish (US)
Pages (from-to)2700-2707
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number4
DOIs
StatePublished - Jan 28 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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