FEBS Letters 2010-09-24

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

Matthias Desch, Elisabeth Schinner, Frieder Kees, Franz Hofmann, Roland Seifert, Jens Schlossmann

Index: FEBS Lett. 584(18) , 3979-84, (2010)

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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.Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.