ABSTRACT
AKAP450 interacts with several signal transduction enzymes, in addition to protein kinase (PKA), including protein kinase N, protein phosphatase 1, protein phosphatase 2A, and the immature nonphosphorylated form of protein kinase Cε. The intracellular targeting and compartmentation of PKA is controlled through association with A-kinase anchoring proteins. Cyclic adenosine monophosphate generation and degradation are regulated by the adenylyl cyclase and phosphodiesterase (PDE) families of enzymes. PDEs contribute to establishing local gradients of cyclic nucleotides by localizing to subcellular compartments and by recruiting into multiprotein signaling complexes. The distribution of PDEs to different subcellular localizations was proposed early on by the observation that PDE activity was found in both the soluble and particulate fractions of the cell. The muscle A-kinase anchoring protein assembles a signal complex consisting of PKA and PDE4D3 at the nuclear envelope, the sarcoplasmic reticulum of cardiomyocytes, and intercalated disks in adult rat heart tissue.
