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Inhibition of phospholipase C-beta1-mediated signaling by O-GlcNAc modification.

Kim YH, Song M, Oh YS, Heo K, Choi JW, Park JM, Kim SH, Lim S, Kwon HM, Ryu SH, Suh PG

Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea.

Here we report inhibition of phospholipase C-beta1 (PLC-beta1)-mediated signaling by post-translational glycosylation with beta-N-acetylglucosamine (O-GlcNAc modification). In C2C12 myoblasts, isoform-specific knock-down experiments using siRNA showed that activation of bradykinin (BK) receptor led to stimulation of PLC-beta1 and subsequent intracellular Ca2+ mobilization. In C2C12 myotubes, O-GlcNAc modification of PLC-beta1 was markedly enhanced in response to treatment with glucosamine (GlcNH2), an inhibitor of O-GlcNAase (PUGNAc) and hyperglycemia. This was associated with more than 50% inhibition of intracellular production of IP3 and Ca2+ mobilization in response to BK. Since the abundance of PLC-beta1 remained unchanged, these data suggest that O-GlcNAc modification of PLC-beta1 led to inhibition of its activity. Moreover, glucose uptake stimulated by BK was significantly blunted by treatment with PUGNAc. These data support the notion that O-GlcNAc modification negatively modulates the activity of PLC-beta1.

Published 3 April 2006 in J Cell Physiol, 207(3): 689-96.
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