Modulation of beta-Catenin Signaling by Glucagon Receptor Activation

doi:10.1371/journal.pone.0033676

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	Modulation of beta-Catenin Signaling by Glucagon Receptor Activation
	Ke, Jiyuan 1; Zhang, Chenghai 1; Harikumar, Kaleeckal G.2; Zylstra-Diegel, Cassandra R.4; Wang, Liren 1; Mowry, Laura E.4; Miller, Laurence J.2; Williams, Bart O.4; Xu, H. Eric1,3
刊名	PLOS ONE
	2012-03-16
卷号	7 期号:3
ISSN号	1932-6203
DOI	10.1371/journal.pone.0033676
文献子类	Article
英文摘要	The glucagon receptor (GCGR) is a member of the class B G protein-coupled receptor family. Activation of GCGR by glucagon leads to increased glucose production by the liver. Thus, glucagon is a key component of glucose homeostasis by counteracting the effect of insulin. In this report, we found that in addition to activation of the classic cAMP/protein kinase A (PKA) pathway, activation of GCGR also induced beta-catenin stabilization and activated beta-catenin-mediated transcription. Activation of beta-catenin signaling was PKA-dependent, consistent with previous reports on the parathyroid hormone receptor type 1 (PTH1R) and glucagon-like peptide 1 (GLP-1R) receptors. Since low-density-lipoprotein receptor-related protein 5 (Lrp5) is an essential co-receptor required for Wnt protein mediated beta-catenin signaling, we examined the role of Lrp5 in glucagon-induced beta-catenin signaling. Cotransfection with Lrp5 enhanced the glucagon-induced beta-catenin stabilization and TCF promoter-mediated transcription. Inhibiting Lrp5/6 function using Dickkopf-1(DKK1) or by expression of the Lrp5 extracellular domain blocked glucagon-induced beta-catenin signaling. Furthermore, we showed that Lrp5 physically interacted with GCGR by immunoprecipitation and bioluminescence resonance energy transfer assays. Together, these results reveal an unexpected crosstalk between glucagon and beta-catenin signaling, and may help to explain the metabolic phenotypes of Lrp5/6 mutations.
资助项目	National Institutes of Health (NIH)[R21RR024887] ; National Institutes of Health (NIH)[R01DK46577] ; National Institutes of Health (NIH)[5R01GM087413] ; Jay and Betty Van Andel Foundation[00000000]
WOS关键词	PROTEIN-COUPLED RECEPTORS ; PARATHYROID-HORMONE ; CELL-GROWTH ; WNT ; PATHWAY ; METABOLISM ; MECHANISMS ; MEMBRANE ; DISEASE ; FAMILY
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000303309100085
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278149]
专题	药物靶标结构与功能中心
通讯作者	Ke, Jiyuan
作者单位	1.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 2.Mayo Clin Scottsdale, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ USA 3.Chinese Acad Sci, Shanghai Inst Mat Med, VARI SIMM Ctr, Ctr Struct & Funct Drug Targets, Shanghai 200031, Peoples R China; 4.Van Andel Res Inst, Lab Cell Signaling & Carcinogenesis, Grand Rapids, MI USA;
推荐引用方式 GB/T 7714	Ke, Jiyuan,Zhang, Chenghai,Harikumar, Kaleeckal G.,et al. Modulation of beta-Catenin Signaling by Glucagon Receptor Activation[J]. PLOS ONE,2012,7(3).
APA	Ke, Jiyuan.,Zhang, Chenghai.,Harikumar, Kaleeckal G..,Zylstra-Diegel, Cassandra R..,Wang, Liren.,...&Xu, H. Eric.(2012).Modulation of beta-Catenin Signaling by Glucagon Receptor Activation.PLOS ONE,7(3).
MLA	Ke, Jiyuan,et al."Modulation of beta-Catenin Signaling by Glucagon Receptor Activation".PLOS ONE 7.3(2012).