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Cyclic cytidine 3′,5′‐monophosphate (cCMP) signals via cGMP kinase I
Author(s) -
Desch Matthias,
Schinner Elisabeth,
Kees Frieder,
Hofmann Franz,
Seifert Roland,
Schlossmann Jens
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.07.059
Subject(s) - intracellular , microbiology and biotechnology , kinase , chemistry , signal transduction , second messenger system , protein kinase a , biochemistry , biology
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.