AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of beta-catenin at Ser 552.
AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent studies show that AMPK involves in cell differentiation but the underlying mechanism remains undefined. Wingless Int-1 (Wnt)/beta-catenin signaling pathway regulates the differentiation of mesenchymal stem cells through enhancing beta-catenin/T-cell transcription factor 1 (TCF) mediated transcription. The objective of this study was to determine whether AMPK cross-talks with Wnt/beta-catenin signaling through phosphorylation of beta-catenin. C3H10T1/2 mesenchymal cells were used. Chemical inhibition of AMPK and the expression of a dominant negative AMPK decreased phosphorylation of beta-catenin at Ser 552. The beta-catenin/TCF mediated transcription was correlated with AMPK activity. In vitro, pure AMPK phosphorylated beta-catenin at Ser 552 and the mutation of Ser 552 to Ala prevented such phosphorylation, which was further confirmed using [gamma-(32)P]ATP autoradiography. In conclusion, AMPK phosphorylates beta-catenin at Ser 552, which stabilizes beta-catenin, enhances beta-catenin/TCF mediated transcription, expanding AMPK from regulation of energy metabolism to cell differentiation and development via cross-talking with the Wnt/beta-catenin signaling pathway.
Zhao
Junxing
J
Developmental Biology Group, Department of Animal Science, College of Agriculture, University of Wyoming, Laramie, WY 82071, USA.
Yue
Wanfu
W
Zhu
Mei J
MJ
Sreejayan
Nair
N
Du
Min
M
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002460:Cell Line; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D051155:Wnt1 Protein / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin; D012694:Serine; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases