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doi:10.1016/j.jmb.2007.09.035 Available online at wwwIntroduction The adenosine 3′, 5 ′ cyclic monophosphate (cAMP) signaling pathway plays a critical role in the cell, serving to transduce the action of a wide variety of hormonal stimuli across species ranging from bacteria to mammals.1 In most eukaryotic cells, cAMP exerts a broad influence inside the cell primarily through its activation of protein kinase A (PKA), a key enzyme with numerous intracellular substrates.2 PKA is a master switch that controls a wide range of cellular functions, which are in turn regulated by cAMP. In the absence of cAMP, PKA exists in an inactive state as a tetrameric holoenzyme composed of a homodimeric regulatory (R) subunit and two catalytic (C) subunits. Binding of cAMP *Corresponding author. E-mail address