title: AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of beta-catenin at Ser 552.
abstract: 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.
authors.affiliation: Developmental Biology Group, Department of Animal Science, College of Agriculture, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Junxing
authors.initials: J
authors.lastname: Zhao
authors.forename: Wanfu
authors.initials: W
authors.lastname: Yue
authors.forename: Mei J
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Nair
authors.initials: N
authors.lastname: Sreejayan
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: 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*
chemical_list: D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin; D012694:Serine; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases