Inhibition of phospholipase C-β1-mediated signaling by O-GlcNAc modification

✍ Scribed by Yun-Hee Kim; Minseok Song; Young-Seok Oh; Kyun Heo; Jung-Woong Choi; Ji-Man Park; Sun-Hee Kim; Seyoung Lim; H. Moo Kwon; Sung Ho Ryu; Pann-Ghill Suh

• Book ID: 102315322
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 446 KB
• Volume: 207
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20609

✦ Synopsis

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 Ca^2+^ mobilization. In C2C12 myotubes, O‐GlcNAc modification of PLC‐β1 was markedly enhanced in response to treatment with glucosamine (GlcNH~2~), an inhibitor of O‐GlcNAase (PUGNAc) and hyperglycemia. This was associated with more than 50% inhibition of intracellular production of IP~3~ and Ca^2+^ 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.