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Inhibition of phospholipase C‐β1‐mediated signaling by O ‐GlcNAc modification
Author(s) -
Kim YunHee,
Song Minseok,
Oh YoungSeok,
Heo Kyun,
Choi JungWoong,
Park JiMan,
Kim SunHee,
Lim Seyoung,
Kwon H. Moo,
Ryu Sung Ho,
Suh PannGhill
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20609
Subject(s) - phospholipase c , chemistry , intracellular , bradykinin , stimulation , c2c12 , signal transduction , phospholipase , receptor , microbiology and biotechnology , enzyme , biochemistry , endocrinology , myogenesis , biology , gene
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.