title: Interaction of Epac with Non-canonical Cyclic Nucleotides.
abstract: Epac1 and Epac2 are cyclic nucleotide-binding (CNB) domain containing proteins, which were originally identified as cAMP-regulated guanine nucleotide exchange factors (GEFs) for the small G-protein Rap. Therefore, Epac proteins founded next to protein kinase A (PKA) and cyclic nucleotide-regulated ion channels the third group of cAMP-responsive proteins in higher organisms. Epac proteins are involved in the regulation of several physiological processes. In particular Epac1 mediates the regulation of molecular processes underlying cell adhesion and mobility. In the pancreas activation of Epac2 potentiates the release of glucose-induced insulin secretion and received attention as a putative target for antidiabetic treatment. While the regulation of Epac by cAMP has been analysed in structural and biochemical detail, less is known on the interaction of Epac with non-canonical cyclic nucleotides. This chapter will discuss to what extent other cyclic purines than cAMP or cyclic pyrimidine could act as Epac agonists or antagonists. The focus will be on the biophysical analysis of the interaction between Epac and these cyclic nucleotides.
authors.affiliation: Molecular Cancer Research and Cancer Genomics Netherlands, Center for Molecular Medicine, UMC Utrecht, Utrecht, The Netherlands. h.rehmann@umcUtrecht.nl.
authors.forename: Holger
authors.initials: H
authors.lastname: Rehmann
mesh_terms: D000818:Animals; D001665:Binding Sites; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D011485:Protein Binding; D015290:Second Messenger Systems
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D009712:Nucleotides, Cyclic; C116122:RAPGEF3 protein, human; C442864:RAPGEF4 protein, human
keywords: Epac; Guanine nucleotide exchange factor; Rap; RapGEF; Small G-protein