The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake
Wang, Fang1,4; Yang, Xiaoyan1,5; Lu, Yanting1,4; Li, Zhenghui2; Xu, Yuhui1; Hu, Jing1; Liu, Jikai2; Xiong, Wenyong1,3
Corresponding AuthorLiu, Jikai(liujikai@mail.scuec.edu.cn) ; Xiong, Wenyong(xiong.wenyong@mail.kib.ac.cn)
2019-07-05
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
Volume294Issue:27Pages:10415-10427
AbstractHypoglycemic drugs such as metformin increase glucose uptake and utilization by peripheral tissues to maintain glucose homeostasis, and the AMP-activated protein kinase (AMPK) signaling pathway is an important component of this pharmacological activity. Liver kinase B1 (LKB1) acts as a kinase upstream of AMPK and plays an important regulatory role in glucose metabolism. In recent years, as a tumor suppressor, LKB1's antitumor activity has been widely studied, yet its hypoglycemic activity is not clear. Here, using biochemical and cell viability assays, site-directed mutagenesis, immunoblotting, and immunofluorescence staining, we found that a natural product, antroalbol H isolated from the basidiomycete mushroom Antrodiella albocinnamomea, increases cellular glucose uptake in murine L6 myotubes and 3T3-L1 adipocytes. Of note, our results indicated that this effect is related to LKB1-mediated Thr-172 phosphorylation of AMPK alpha. Furthermore, we observed that antroalbol H induces the phosphorylation of LKB1 specifically at Thr-189 and changes subcellular localization of LKB1. Finally, antroalbol H treatment strikingly promoted glucose transporter type 4 (GLUT4) translocation to the plasma membrane. We conclude that antroalbol H promotes Thr-189 phosphorylation of LKB1, leading to AMPK activation, revealing this residue as a potential target for increasing glucose uptake, and that antroalbol H therefore has potential for managing hyperglycemia.
Keywordglucose metabolism liver kinase B1 (LKB1) AMP-activated kinase (AMPK) glucose transporter type 4 (GLUT4) fungi Basidiomycete diabetes energy sensing glucose homeostasis sesquiterpene
DOI10.1074/jbc.RA118.007231
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000478717100004
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/68151
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorLiu, Jikai; Xiong, Wenyong
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430074, Hubei, Peoples R China
3.Ningxia Med Univ, Gen Hosp, Yinchuan 750004, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Kunming Univ Sci & Technol, Fac Life Sci & Technol, Kunming 650201, Yunnan, Peoples R China
Recommended Citation
GB/T 7714
Wang, Fang,Yang, Xiaoyan,Lu, Yanting,et al. The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(27):10415-10427.
APA Wang, Fang.,Yang, Xiaoyan.,Lu, Yanting.,Li, Zhenghui.,Xu, Yuhui.,...&Xiong, Wenyong.(2019).The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake.JOURNAL OF BIOLOGICAL CHEMISTRY,294(27),10415-10427.
MLA Wang, Fang,et al."The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake".JOURNAL OF BIOLOGICAL CHEMISTRY 294.27(2019):10415-10427.
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