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

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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)689-696
Number of pages8
JournalJournal of cellular physiology
Volume207
Issue number3
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Dive into the research topics of 'Inhibition of phospholipase C-β1-mediated signaling by O-GlcNAc modification'. Together they form a unique fingerprint.

Cite this