期刊
JOURNAL OF BIOCHEMISTRY
卷 143, 期 3, 页码 359-367出版社
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvm228
关键词
glycogen synthase; glycogen synthase kinase 3; heparin; myelin basic protein; phospholipid; sulfatide; tau-kinase; tau protein
The stimulatory effects of SH (sulfatide and heparin) and two phospholipids (PI and PS) on autophosphorylation of GSK-3 beta and the GSK-3 beta-mediated phosphorylation of myelin basic protein (MBP) and two synthetic MBP peptides (M86 and M156) were comparatively examined in vitro. It was found that (i) both PI and SH highly stimulated the GSK-3 beta-mediated phosphorylation of MBP, but not glycogen synthase, and two MBP peptides through their direct binding to these substrates and (ii) both PI and heparin, as compared with sulfatide, highly stimulated autophosphorylation of GSK-3 beta. The K-m value of MBP for GSK-3 beta was highly reduced and the V-max value was significantly increased in the presence of these acidic modulators, which augmented further phosphorylation of MIBP by the kinase. Under our experimental condition, similar stimulatory effects of PI and heparin were observed with the GSK-3 beta-mediated phosphorylation of tau protein (TP) in vitro. These results presented here suggest that these two phospholipids and SH may function as effective stimulators for autophosphorylation of GSK-3 beta and for the GSK-3 beta-mediated high phosphorylation of SH-binding proteins, including MBP and TP, in the highly accumulated levels of these acidic and sulfated modulators in the brain.
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