Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway.
beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation.
Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
William G
WG
Aschenbach
Richard C
RC
Ho
Kei
K
Sakamoto
Nobuharu
N
Fujii
Yangfeng
Y
Li
Young-Bum
YB
Kim
Michael F
MF
Hirshman
Laurie J
LJ
Goodyear
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D000072261:Dishevelled Proteins; D006003:Glycogen / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000096:biosynthesis* / Q000378:metabolism; D000099293:Protein Kinase C-lambda
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D006003:Glycogen; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin; D007527:Isoenzymes; D010750:Phosphoproteins; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D051176:beta Catenin; D000099293:Protein Kinase C-lambda; C000605508:Gsk3b protein, rat