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

Surajit Ganguly; Jonathan A. Gastel; Joan L. Weller; Christian Schwartz; Howard Jaffe; M. A.A. Namboodiri; Steven L. Coon; Alison B. Hickman; Mark Rollag; Tomas Obsil; Philippe Beauverger; Gilles Ferry; Jean A. Boutin; David C. Klein

doi:10.1073/pnas.141118798

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

Surajit Ganguly
, Jonathan A. Gastel
, Joan L. Weller
, Christian Schwartz
, Howard Jaffe
, M. A.A. Namboodiri
, Steven L. Coon
, Alison B. Hickman
, Mark Rollag
, Tomas Obsil
, Philippe Beauverger
, Gilles Ferry
, Jean A. Boutin
, David C. Klein^*

^*Corresponding author for this work

Anatomy, Physiology, and Genetics

Research output: Contribution to journal › Article › peer-review

176 Scopus citations

Abstract

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 2.3.1.87). 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.

Original language	English
Pages (from-to)	8083-8088
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	98
Issue number	14
DOIs	https://doi.org/10.1073/pnas.141118798
State	Published - 2001

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Ganguly, S., Gastel, J. A., Weller, J. L., Schwartz, C., Jaffe, H., Namboodiri, M. A. A., Coon, S. L., Hickman, A. B., Rollag, M., Obsil, T., Beauverger, P., Ferry, G., Boutin, J. A., & Klein, D. C. (2001). Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis. Proceedings of the National Academy of Sciences of the United States of America, 98(14), 8083-8088. https://doi.org/10.1073/pnas.141118798

@article{5ae48420f53f4cafba682256df5e1c78,

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

abstract = "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 2.3.1.87). 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 Km for 5-hydroxytryptamine (serotonin). Similar switches could play a role in cAMP signal transduction in other biological systems.",

author = "Surajit Ganguly and Gastel, \{Jonathan A.\} and Weller, \{Joan L.\} and Christian Schwartz and Howard Jaffe and Namboodiri, \{M. A.A.\} and Coon, \{Steven L.\} and Hickman, \{Alison B.\} and Mark Rollag and Tomas Obsil and Philippe Beauverger and Gilles Ferry and Boutin, \{Jean A.\} and Klein, \{David C.\}",

year = "2001",

doi = "10.1073/pnas.141118798",

language = "English",

volume = "98",

pages = "8083--8088",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "14",

}

Ganguly, S, Gastel, JA, Weller, JL, Schwartz, C, Jaffe, H, Namboodiri, MAA, Coon, SL, Hickman, AB, Rollag, M, Obsil, T, Beauverger, P, Ferry, G, Boutin, JA & Klein, DC 2001, 'Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 14, pp. 8083-8088. https://doi.org/10.1073/pnas.141118798

TY - JOUR

T1 - Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis

AU - Ganguly, Surajit

AU - Gastel, Jonathan A.

AU - Weller, Joan L.

AU - Schwartz, Christian

AU - Jaffe, Howard

AU - Namboodiri, M. A.A.

AU - Coon, Steven L.

AU - Hickman, Alison B.

AU - Rollag, Mark

AU - Obsil, Tomas

AU - Beauverger, Philippe

AU - Ferry, Gilles

AU - Boutin, Jean A.

AU - Klein, David C.

PY - 2001

Y1 - 2001

N2 - 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 2.3.1.87). 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 Km for 5-hydroxytryptamine (serotonin). Similar switches could play a role in cAMP signal transduction in other biological systems.

AB - 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 2.3.1.87). 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 Km for 5-hydroxytryptamine (serotonin). Similar switches could play a role in cAMP signal transduction in other biological systems.

UR - https://www.scopus.com/pages/publications/0034944881

U2 - 10.1073/pnas.141118798

DO - 10.1073/pnas.141118798

M3 - Article

C2 - 11427721

AN - SCOPUS:0034944881

SN - 0027-8424

VL - 98

SP - 8083

EP - 8088

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 14

ER -

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

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