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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / enzymology
  • Aorta / physiology
  • Cyclic CMP / metabolism*
  • Cyclic CMP / pharmacology
  • Cyclic GMP-Dependent Protein Kinases / genetics
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Mice
  • Mice, Knockout
  • Muscle Relaxation*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / enzymology
  • Muscle, Smooth / physiology*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / physiology
  • Signal Transduction


  • Inositol 1,4,5-Trisphosphate Receptors
  • Cyclic CMP
  • Cyclic GMP-Dependent Protein Kinases