The cyclic AMP-protein kinase A (cAMP-PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells. A kinase anchoring proteins (AKAPs) target PKA to specific substrates and distinct subcellular compartments providing spatial and temporal specificity for mediation of biological effects channeled through the cAMP-PKA pathway. We have recently identified new AKAP-coordinated signaling complexes in heart cells, adipocytes, placental trophoblasts and immune cells. In adipose tissue a new AKAP, Opa1, on lipid droplets coordinates phosphorylation of perilipin and adrenergic control of lipolysis. In the differentiation of the human placenta, ezrin directs PKA to a molecular complex of connexin 43 (Cx43) and zona occludens-1 (ZO-1), two proteins previously shown to form gap junctions implicated in cell fusion. We demonstrate that ezrin-mediated coordination of PKA and Cx43 localization is necessary for discrete control of Cx43 phosphorylation and cAMP-regulated gap junction communication.