Cyclic AMP-independent Activation of Protein Kinase A by Vasoactive Peptides

Nickolai O. Dulin, Jiaxin Niu, Darren D Browning, Richard D. Ye, Tatyana Voyno-Yasenetskaya

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Protein kinase A (PKA) is an important effector enzyme commonly activated by cAMP. The present study focuses on our finding that the vasoactive peptide endothelin-1 (ET1), whose signaling is not coupled to cAMP production, stimulates PKA in two independent cellular models. Using an in vivo assay for PKA activity, we found that ET1 stimulated PKA in HeLa cells overexpressing ET1 receptors and in aortic smooth muscle cells expressing endogenous levels of ET1 receptors. In these cell models, ET1 did not stimulate cAMP production, indicating a novel mechanism for PKA activation. The ETl-induced activation of PKA was found to be dependent on the degradation of inhibitor of κB, which was previously reported to bind and inhibit PKA. ET1 potently stimulated the nuclear factor-κB pathway, and this effect was inhibited by overexpression of the inhibitor of κB dominant negative mutant (IκBαm) and by treatment with the proteasome inhibitor MG-132. Importantly, IκBαm and MG-132 had similar inhibitory effects on ET1-induced activation of PKA without affecting Gs-mediated activation of PKA or ET1-induced phosphorylation of mitogen-activated protein kinase. Finally, another vasoactive peptide, angiotensin II, also stimulated PKA in a cAMP-independent manner in aortic smooth muscle cells. These findings suggest that cAMP-independent activation of PKA might be a general response to vasoactive peptides.

Original languageEnglish (US)
Pages (from-to)20827-20830
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
StatePublished - Jun 15 2001
Externally publishedYes

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Cyclic AMP-Dependent Protein Kinases
Cyclic AMP
Chemical activation
Peptides
Endothelin-1
Endothelin A Receptors
Smooth Muscle Myocytes
Muscle
Cells
Phosphorylation
Proteasome Inhibitors
Corrosion inhibitors
Mitogen-Activated Protein Kinases
HeLa Cells
Angiotensin II
Assays
Degradation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cyclic AMP-independent Activation of Protein Kinase A by Vasoactive Peptides. / Dulin, Nickolai O.; Niu, Jiaxin; Browning, Darren D; Ye, Richard D.; Voyno-Yasenetskaya, Tatyana.

In: Journal of Biological Chemistry, Vol. 276, No. 24, 15.06.2001, p. 20827-20830.

Research output: Contribution to journalArticle

Dulin, Nickolai O. ; Niu, Jiaxin ; Browning, Darren D ; Ye, Richard D. ; Voyno-Yasenetskaya, Tatyana. / Cyclic AMP-independent Activation of Protein Kinase A by Vasoactive Peptides. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 24. pp. 20827-20830.
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