Protein kinase C activation down-regulates natriuretic peptide receptor C expression via transcriptional and post-translational pathways

FEBS Letters
N YanakaK Omori

Abstract

Natriuretic peptide receptor C (NPR-C) mRNA expression and ANP-binding activity via NPR-C are significantly down-regulated in HeLa cells with phorbol myristate acetate (PMA) treatment. Stabilization of the NPR-C mRNA by PMA indicated that down-regulation of its mRNA was mediated through negative transcriptional regulation. Despite the significant loss of the mRNA, reduction of NPR-C-specific ANP-binding activity after PMA exposure (4 h) was accompanied by a slight decrease in total NPR-C protein (with a 5% loss) and was also produced in the presence of actinomycin D or cycloheximide. The inhibitory effect of a long PMA exposure (18 h) paralleled with a decrease in total NPR-C protein is suggested to be dependent on reduction of de novo NPR-C synthesis. PMA-induced transcriptional and post-translational down-regulation of NPR-C was effectively reversible in the presence of the protein kinase C inhibitor GF109203X. These findings demonstrate that protein kinase C activation down-regulated NPR-C expression through transcriptional and post-translational pathways and that immediate functional receptor loss was mediated via a post-translational mechanism, such as enhanced receptor internalization.

References

Apr 30, 1990·Biochemical and Biophysical Research Communications·T SudohH Matsuo
Sep 14, 1990·Biochemical and Biophysical Research Communications·J G PorterJ A Lewicki
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Citations

Jul 2, 2003·Archives of Biochemistry and Biophysics·Malika BoumatiMadhu B Anand-Srivastava
Mar 30, 2001·European Journal of Biochemistry·N RoyS S Visweswariah
Jul 2, 2003·Bioscience, Biotechnology, and Biochemistry·Noriyuki YanakaKenji Omori
Jun 19, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·J Z SunY F Chen
Jun 21, 2006·Molecular and Cellular Biochemistry·William R GowerSuzanne M Solivan
Jun 11, 2002·Archives of Biochemistry and Biophysics·Malika BoumatiMadhu B Anand-Srivastava

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