Inhibition of phospholipase C-beta1-mediated signaling by O-GlcNAc modification.
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.
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea.
Yun-Hee
YH
Kim
Minseok
M
Song
Young-Seok
YS
Oh
Kyun
K
Heo
Jung-Woong
JW
Choi
Ji-Man
JM
Park
Sun-Hee
SH
Kim
Seyoung
S
Lim
H Moo
HM
Kwon
Sung Ho
SH
Ryu
Pann-Ghill
PG
Suh
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002413:Cations, Divalent / Q000737:chemistry; D002460:Cell Line; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D032446:Myoblasts / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D054799:Phospholipase C beta; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D002413:Cations, Divalent; D007527:Isoenzymes; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; D005947:Glucose; D001920:Bradykinin; D002118:Calcium; D000117:Acetylglucosamine