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- Title
Cyclic cytidine 3′,5′-monophosphate (cCMP) signals via cGMP kinase I
- Authors
Desch, Matthias; Schinner, Elisabeth; Kees, Frieder; Hofmann, Franz; Seifert, Roland; Schlossmann, Jens
- Abstract
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.
- Subjects
BLOOD platelet aggregation; CELLULAR signal transduction; PROTEIN kinases; AORTA abnormalities; LABORATORY mice; MOLECULES
- Publication
FEBS Letters, 2010, Vol 584, Issue 18, p3979
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2010.07.059