Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis

The daily rhythm in melatonin levels is controlled by cAMP through actions on the penultimate enzyme in melatonin synthesis, arylalkylamine IV-acetylt ransferase (AANAT; serotonin IV-acetyltransferase, EC 2.3.1.87). Results pr esented here describe a regulatory/binding sequence in AANAT that encodes a cAMP-operated binding switch through which cAMP-regulated protein kinase-c atalyzed phosphorylation [RRHTLPAN --> RRHpTLPAN] promotes formation of a c omplex with 14-3-3 proteins. Formation of this AANAT/14-3-3 complex enhance s melatonin production by shielding AANAT from dephosphorylation and/or pro teolysis and by decreasing the K-m for 5-hydroxytryptamine (serotonin). Sim ilar switches could play a role in cAMP signal transduction in other biolog ical systems.