Inhibition of phospholipase C-beta1-mediated signaling by O-GlcNAc modification |
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Authors: | Kim Yun-Hee Song Minseok Oh Young-Seok Heo Kyun Choi Jung-Woong Park Ji-Man Kim Sun-Hee Lim Seyoung Kwon H Moo Ryu Sung Ho Suh Pann-Ghill |
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Institution: | Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea. |
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Abstract: | 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. |
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