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

FEBS Letters

Akatsuka, Hiroyuki¹  Omori, Kenji¹  Yanaka, Noriyuki¹ 

[1] Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., 16-89 Kashima-3-chome, Yodogawa-ku, Osaka 532, Japan

关键词: Natriuretic peptide;    Natriuretic peptide clearance receptor;    Phorbol myristate acetate;    Down-regulation;    Post-translational pathway;    ANP;    atrial natriuretic peptide;    NPR-C;    natriuretic peptide receptor C;    PKC;    protein kinase C;    PMA;    phorbol myristate acetate;    GAPDH;    glyceraldehyde phosphate dehydrogenase;   

DOI  :  10.1016/S0014-5793(97)01406-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown