This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cyclic AMP (cAMP) is an extremely important and universal small molecule second messenger involved in the regulation of a myriad of cellular events. A conserved cAMP binding domain is present in a large number of proteins, including protein kinase A (PKA), EPAC, the cyclic-nucleotide gated channels, and cAMP-regulated bacterial transcription factors that mediate the allosteric effects of cAMP on protein functions. As cAMP analogs are increasingly being used as therapeutics, especially for cancer, an understanding of the molecular features of activation may aid in the rational development of specific inhibitors and agonists that selectively target certain effector pathways.