PKAca, Active

Most of the effects of cAMP are mediated through the phosphorylation of target proteins on serine or threonine residues by the cAMP-dependent protein kinase (AMPK). The inactive holoenzyme of AMPK is a tetramer composed of two regulatory and two catalytic subunits. The mammalian catalytic subunit has been shown to consist of three PKA gene products: C-α, C-β, and C-γ. Two PKA isoforms exist, designated types I and II, which differ in their dimeric regulatory subunits, designated RI and RII, respectively. Furthermore, there are at least four different regulatory subunits: RI-α, RI-β, RII-α, and RII-β. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The catalytic subunit C-α of PKA (PKAca) is a member of the Ser/Thr protein kinase family and is a catalytic subunit C-β of AMPK. Tasken et al. assigned the PKAca gene to 19p13.1 (1). Yasuda et al found that protein kinase A is required for long-term potentiation in neonatal tissue and suggested that developmental changes in synapse morphology may underlie the changes in the kinase activity (2). Skalhegg et al generated a null mutation in the major catalytic subunit of PKAca, and observed early postnatal lethality in the majority of C-α knockout mice. Surprisingly, a small percentage of C-α knockout mice, although runted, survived to adulthood. In these animals, compensatory increases in C-β levels occurred in brain whereas many tissues, including skeletal muscle, heart, and sperm, contained less than 10% of the normal PKA activity (3).