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 N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC ). Results presented here describe a regulatory/binding sequence in AANAT that encodes a cAMP-operated binding switch through which cAMP-regulated protein kinase-catalyzed phosphorylation [RRHTLPAN --> RRHpTLPAN] promotes formation of a complex with 14-3-3 proteins. Formation of this AANAT/14-3-3 complex enhances melatonin production by shielding AANAT from dephosphorylation and/or proteolysis and by decreasing the K(m) for 5-hydroxytryptamine (serotonin). Similar switches could play a role in cAMP signal transduction in other biological systems.
Ganguly
S
S
Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA.
Gastel
J A
JA
Weller
J L
JL
Schwartz
C
C
Jaffe
H
H
Namboodiri
M A
MA
Coon
S L
SL
Hickman
A B
AB
Rollag
M
M
Obsil
T
T
Beauverger
P
P
Ferry
G
G
Boutin
J A
JA
Klein
D C
DC
D048948:14-3-3 Proteins; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase; D001191:Arylamine N-Acetyltransferase / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008550:Melatonin / Q000502:physiology*; D010870:Pineal Gland / Q000502:physiology*; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000502:physiology*
D048948:14-3-3 Proteins; D014446:Tyrosine 3-Monooxygenase; D001191:Arylamine N-Acetyltransferase; C478879:AANAT protein, human; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin