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

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• 作者：Matthias Desch ; Elisabeth Schinner ; Frieder Kees ; Franz Hofmann ; Rol ; Seifert ; Jens Schlossmann
• 关键词：cCMP ; cGMP ; Cyclic nucleotide ; Signal transduction ; Smooth muscle ; Platelet
• 刊名：FEBS Letters
• 出版年：2010
• 出版时间：24 September 2010
• 年：2010
• 卷：584
• 期：18
• 页码：3979-3984
• 全文大小：531 K

文摘

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.