Protein-Kinase A and Human Disease: The Core of cAMP-Dependent Signaling in Health and Disease

This report summarizes several aspects of protein kinase A (PKA) signaling and its involvement in health and disease. It follows the discovery that PRKAR1A, the gene that codes for the relatively abundant regulatory subunit type 1A of protein kinase A, is the tumor suppressor gene responsible for the multiple endocrine neoplasia syndrome known as "Carney complex." Although cyclic AMP (cAMP)-dependent signaling has already been found to be involved in the pathogenesis of other genetic conditions predisposing to tumor development, this is the first time that PKA itself was directly involved in tumorigenesis and, perhaps, carcinogenesis in an inherited disease.