The ability of cells to respond to hormones, growth factors, and neurotransmitters is a prerequisite for life. A better understanding of the cellular events involved in relaying the signals conveyed by these factors may contribute to improved health. Many of these factors are ligands for G protein-coupled receptors which can increase cyclic adenosine 3', 5'-monophosphate (cAMP) and activate cAMP-dependent protein kinase (PKA). PKA is a holoenzyme consisting of two regulatory (R) and two catalytic (C) subunits. Upon the binding of 4 cAMP molecules to an R dimer, the C subunits are released to phosphorylate target proteins. Many proteins are substrates for phosphorylation by PKA, yet it is unclear how the hormonal activation of PKA results in the preferential phosphorylation of certain target proteins. The goal of this research proposal is to study the unique function of those regulatory subunits of PKA that anchor PKA to subcellular compartments and that may, therefore, serve to direct the phosphorylation of those proteins that are in close proximity to PKA. By creating mouse models with a null mutation in one of these regulatory subunits, I will be able to address the unique role played by this regulatory subunit in the physiological responses, for example, of the heart during beta-adrenergic stimulation, of the hippocampus during learning and memory, and of the testis during spermatogenesis.