1. Inhibition of phospholipase C-beta1-mediated signaling by O-GlcNAc modification
- Author
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Seyoung Lim, Young Seok Oh, Jung Woong Choi, H. Moo Kwon, Pann-Ghill Suh, Ji Man Park, Yun-Hee Kim, Minseok Song, Kyun Heo, Sung Ho Ryu, and Sun Hee Kim
- Subjects
medicine.medical_specialty ,Glycosylation ,Physiology ,Cations, Divalent ,Glucose uptake ,Clinical Biochemistry ,Muscle Fibers, Skeletal ,Phospholipase C beta ,Bradykinin ,Phospholipase ,Biology ,Acetylglucosamine ,Cell Line ,Myoblasts ,chemistry.chemical_compound ,Mice ,Internal medicine ,medicine ,Animals ,Receptor ,Phospholipase C ,Cell Biology ,Cell biology ,Isoenzymes ,Endocrinology ,Glucose ,chemistry ,Type C Phospholipases ,Calcium ,C2C12 ,Oxidation-Reduction ,Protein Processing, Post-Translational ,Intracellular ,Signal Transduction - Abstract
Here we report inhibition of phospholipase C-β1 (PLC-β1)-mediated signaling by post-translational glycosylation with β-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-β1 and subsequent intracellular Ca2+ mobilization. In C2C12 myotubes, O-GlcNAc modification of PLC-β1 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-β1 remained unchanged, these data suggest that O-GlcNAc modification of PLC-β1 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-β1. J. Cell. Physiol. © 2006 Wiley-Liss, Inc.
- Published
- 2006