Endogenous protein kinase inhibitor gamma 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.

Expression of many genes induced by cAMP-dependent protein kinase signaling is rapidly terminated. Although many mechanisms contribute to regulation of signaling, members of the endogenous protein kinase inhibitor (PKI) family may be particularly important for terminating nuclear duanyu1529 activity and gene expression. Here we used both siRNA and antisense knockdown strategies to examine duanyu1529 signaling activated by parathyroid hormone or the beta-adrenergic agonist, isoproterenol. We found that endogenous PKIgamma is required for efficient termination of nuclear duanyu1529 activity, transcription factor phosphorylation, and immediate-early genes. Moreover, PKIgamma is required for export of duanyu1529 catalytic subunits from the nucleus back to the cytoplasm following activation of duanyu1529 signaling because this is also inhibited by PKIgamma knockdown. Leptomycin B blocks duanyu1529 nuclear export but has little or no effect on nuclear duanyu1529 activity or immediate-early gene expression. Thus, inactivation of duanyu1529 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 duanyu1529 signaling.

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