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FEBS Lett. 2010 Sep 24;584(18):3979-84. doi: 10.1016/j.febslet.2010.07.059. Epub 2010 Aug 6.

Cyclic cytidine 3',5'-monophosphate (cCMP) signals via cGMP kinase I.

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1
Pharmacology and Toxicology, University Regensburg, Regensburg, Germany.

Abstract

We analysed the function and intracellular signalling of the cyclic pyrimidinic nucleotide cCMP. The membrane-permeable cCMP analogue dibutyryl-cCMP mediated mouse aorta relaxation. cCMP activated purified cGMP-dependent protein kinase (cGK) Iα and Iβ and stimulated cGK in aorta lysates. cCMP-induced relaxation was abolished in cGKI-knockout tissue. Additionally, deletion of inositol-trisphosphate receptor associated cGKI substrate (IRAG) suppressed cCMP-mediated relaxation. Signalling of cCMP via cGKI/IRAG appears to be of broader physiological importance because cCMP-mediated inhibition of platelet aggregation was absent in cGKI- and IRAG-deficient platelets. These results demonstrate that cCMP acts as intracellular messenger molecule, most unexpectedly utilizing the cGMP signal transduction pathway.

PMID:
20691687
DOI:
10.1016/j.febslet.2010.07.059
[Indexed for MEDLINE]
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