松果体环磷酸腺苷（cAMP）调控的芳基烷基胺N - 乙酰转移酶/14-3-3结合开关在褪黑素合成中的作用
Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis.
作者信息
Ganguly S, Gastel J A, Weller J L, Schwartz C, Jaffe H, Namboodiri M A, Coon S L, Hickman A B, Rollag M, Obsil T, Beauverger P, Ferry G, Boutin J A, Klein D C
机构信息
Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8083-8. doi: 10.1073/pnas.141118798. Epub 2001 Jun 26.
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 ). 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.
摘要
褪黑素水平的日常节律是由环磷酸腺苷（cAMP）通过作用于褪黑素合成过程中的倒数第二个酶——芳基烷基胺N - 乙酰基转移酶（AANAT；血清素N - 乙酰基转移酶，EC）来控制的。此处呈现的结果描述了AANAT中的一个调控/结合序列，该序列编码一个cAMP操作的结合开关，通过这个开关，cAMP调节的蛋白激酶催化的磷酸化作用[RRHTLPAN --> RRHpTLPAN]促进了与14 - 3 - 3蛋白形成复合物。这种AANAT/14 - 3 - 3复合物的形成通过保护AANAT不被去磷酸化和/或蛋白水解，并通过降低5 - 羟色胺（血清素）的米氏常数（K(m)）来增强褪黑素的产生。类似的开关可能在其他生物系统的cAMP信号转导中发挥作用。
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