Search for new cyclic AMP‐binding proteins

Abstract

Today, there is evidence that the cAMP-dependent kinases (PKA) are not the only intracellular receptors involved in intracellular cAMP signalling in eukaryotes. Other cAMPbinding proteins have been recently identi¢ed, including some cyclic nucleotide-gated channels and Epac (exchange protein directly activated by cAMP) proteins. All these proteins bind cAMP through conserved cyclic nucleotide monophosphatebinding domains. However, all putative cAMP-binding proteins having such domains, as revealed by computer analysis, do not necessarily bind cAMP, indicating that their presence is not a su⁄cient criteria to predict cAMP-binding property for a protein.

Identification of casein kinase 1, casein kinase 2, and cAMP-dependent protein kinase-like activities in Trypanosoma evansi

“…However, today there is evidence that the cAMP-dependent kinases are not the only intracellular receptors involved in intracellular cAMP signaling in eukaryotes. Other cAMP-binding proteins have been identified, including some cyclic nucleotide-gated channels and Epac (exchange protein directly activated by cAMP) proteins (Dremier et al 2003). Cyclic AMPbinding proteins that do not correspond to the PKA regu-latory subunits have been described in T. cruzi (RangelAldao et al 1988) and in Leishmania (Banerjee & Sarkar 2001).…”

Beyond the dogma: novel β2-adrenoceptor signalling in the airways

“…In addition, there are a number of other signalling processes and proteins that may also be targeted by cAMP-GEFs, indicating the need to elucidate the functional significance of these novel pathways [218]. Nevertheless, cAMP-GEFs are now being widely examined with a view to explaining the increasing number of observations of cAMP-dependent PKA-independent effects, especially since a number of other putative cAMP-binding proteins do not seem to bind cAMP [222].…”

Novel mechanisms of the regulation of Protein kinase B in adipocytes; implications for Protein kinase A, Epac, Phosphodiesterases 3 and 4

“…There are two isoforms of PKA, PKA I and II, which are ubiquitously expressed and play a crucial role in cell metabolism, growth and other functions, through phosphorylation of numerous target proteins [3]. PKAs were thought to be the major effectors of cAMP until the discovery of Epacs, guanine nucleotide exchange factors directly activated by cAMP, which have been shown to activate the small G proteins Rap1 and Rap2 [3]. Epac1 has one and Epac2 has two binding sites for cAMP.…”

“…[4]. Epacs have been shown to affect diverse cellular functions including hormone/ transmitter secretion and cell adhesion [3,4]. Cellular gradients of cAMP are generated by the combined actions of adenylate cyclases and cyclic nucleotide phosphodiesterases (PDEs) [5].…”