Phosphorylation of mouse serine racemase regulates D-serine synthesis.
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.
Foltyn
Veronika N
VN
Department of Biochemistry, B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Zehl
Martin
M
Dikopoltsev
Elena
E
Jensen
Ole N
ON
Wolosker
Herman
H
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000096:biosynthesis* / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D000099300:Serine Racemase
D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase