The second messenger cyclic AMP mediates diverse cellular responses to external signals such as proliferation, ion transport, regulation of metabolism and gene transcription by activation of the cAMP-dependent protein kinase (cAPK or PKA). Activation of PKA occurs when cAMP binds to the two regulatory subunits of the tetrameric PKA holoenzyme resulting in release of active catalytic subunits. One of several regulatory subunits, p-PKA IIβ reg (cAMP-dependent protein kinase type II-beta regulatory subunit), also known as PRKAR2B, is a 418 amino acid protein that is phosphorylated by the activated catalytic chain. p-PKA IIβ reg knockout mice exhibit diminished white adipose tissue and were protected against diet-induced obesity and fatty livers,as well as markedly reduced leptin mRNA. Also playing a role in the immune response, p-PKA IIβ reg suppresses CREB transcriptional activity and down-regulates IL-2 production in T-lymphocytes.