Phosphorylation of mouse serine racemase regulates D-serine synthesis

被引:30
|
作者
Foltyn, Veronika N. [1 ]
Zehl, Martin [2 ,3 ]
Dikopoltsev, Elena [1 ]
Jensen, Ole N. [2 ]
Wolosker, Herman [1 ]
机构
[1] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Biochem, IL-31096 Haifa, Israel
[2] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark
[3] Univ Vienna, Dept Pharmacognosy, A-1090 Vienna, Austria
基金
以色列科学基金会;
关键词
D-Serine; NMDA receptor; Glutamate; Gliotransmission; Serine racemase; NMDA; NEUROTOXICITY;
D O I
10.1016/j.febslet.2010.05.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Serine racemase (SR) catalyses the synthesis of the transmitter/neuromodulator D-serine, which plays a major role in synaptic plasticity and N-methyl D-aspartate receptor neurotoxicity. We now report that SR is phosphorylated at Thr71 and Thr227 as revealed by mass spectrometric analysis and in vivo phosphorylation assays. Thr71 phosphorylation was observed in the cytosolic and membrane- bound SR while Thr227 phosphorylation was restricted to the membrane fraction. The Thr71 site has a motif for proline-directed kinases and is the main phosphorylation site of SR. Experiments with a phosphorylation-deficient SR mutant indicate that Thr71 phosphorylation increases SR activity, suggesting a novel mechanism for regulating D-serine production. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:2937 / 2941
页数:5
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