Email updates

Keep up to date with the latest news and content from BMC Pharmacology and Toxicology and BioMed Central.

This article is part of the supplement: 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access Open Badges Poster presentation

Identification of cCMP binding and activated proteins

Stefanie Wolfertstetter1*, Elisabeth Schinner1, Franz Hofmann2 and Jens Schlossmann1

Author Affiliations

1 Department of Pharmacology and Toxicology, University of Regensburg, Germany

2 FOR923, Institute for Pharmacology and Toxicology, TU, Munich, Germany

For all author emails, please log on.

BMC Pharmacology and Toxicology 2013, 14(Suppl 1):P78  doi:10.1186/2050-6511-14-S1-P78

The electronic version of this article is the complete one and can be found online at:

Published:29 August 2013

© 2013 Wolfertstetter et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


cAMP and cGMP are well established second messengers and essential for numerous of (patho)physiological processes. These purine cyclic nucleotides activate PKA and PKG, respectively. So far, there was no evidence of further cyclic nucleotides acting as second messengers. Meanwhile the existence of cCMP was described [1]. Formation of the cyclic pyrimidine nucleotide cyclic cytidine 3’,5’-monophosphate (cCMP) by cytidylyl cyclases is debated. cCMP induces relaxation of vascular smooth muscle via cGKI [2]. Furthermore, it was postulated that cCMP is relevant for cell growth [3] and blood cell function [4]. However, functions regulated by cCMP are mostly unknown.


Our aim is to identify cCMP-binding and -acitvated proteins and to elucidate whether cCMP plays a role as second messenger. We confirmed that cCMP activates the purified cyclic nucleotide-dependent protein kinases cAK and cGK. Then we investigated the effect of cCMP on purified cyclic nucleotide-dependent protein kinases and on intact tissues of wildtype (WT) and cGKI-knockout (KO) mice, namely jejunum, lung and brain. We identified various protein kinases as cCMP-binding proteins in tissue lysates. cCMP stimulated cyclic GMP-dependent protein kinases in WT tissue lysates, however there was no stimulation of phosphorylation in KO tissue lysates.


These results indicate that cCMP could play a role in physiological processes in jejunum, lung and brain.


  1. Newton RP, Salih SG, Salvage BJ, Kingston EE: Extraction, purification and identification of cytidine 3',5'-cyclic monophosphate from rat tissues.

    Biochem J 1984, 21:665-673. OpenURL

  2. Desch M, Schinner E, Kees F, Hofmann F, Seifert R, Schlossmann : Cyclic cytidine 3',5'-monophosphate (cCMP) signals via cGMP kinase I.

    FEBS Lett 2010, 584:3979-3984. PubMed Abstract | Publisher Full Text OpenURL

  3. Cheng YC, Bloch A: Demonstration, in leukemia L-1210 cells, of a phosphodiesterase acting on 3':5'-cyclic CMP but not on 3':5'-cyclic AMP or 3':5'- cyclic GMP.

    J Biol Chem 1978, 253:2522-2524. PubMed Abstract | Publisher Full Text OpenURL

  4. Ervens J, Seifert R: Differential modulation by N4, 2'-O-dibutyryl cytidine 3':5'-cyclic monophosphate of neutrophil activation.

    Biochem Biophys Res Commun 1991, 74:258-267. OpenURL