AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase

被引：58

作者：

Bang, Sookhee ^{[2
]}

Kim, Seyun ^{[1
]}

Dailey, Megan J. ^{[4
]}

Chen, Yong ^{[2
]}

Moran, Timothy H. ^{[4
]}

Snyder, Solomon H. ^{[1
,4
,5
]}

Kim, Sangwon F. ^{[2
,3
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[2] Univ Penn, Perelman Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA

[4] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 02期

基金：

美国国家卫生研究院;

关键词：

UPSTREAM KINASE; PHOSPHORYLATION; LKB1; PATHWAY; SENSOR; BETA; RHEB;

D O I：

10.1073/pnas.1119751109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

he AMP-activated kinase (AMPK) senses the energy status of cells and regulates fuel availability, whereas hypothalamic AMPK regulates food intake. We report that inositol polyphosphate multikinase (IPMK) regulates glucose signaling to AMPK in a pathway whereby glucose activates phosphorylation of IPMK at tyrosine 174 enabling the enzyme to bind to AMPK and regulate its activation. Thus, refeeding fasted mice rapidly and markedly stimulates transcriptional enhancement of IPMK expression while down-regulating AMPK. Also, AMPK is up-regulated in mice with genetic depletion of hypothalamic IPMK. IPMK physiologically binds AMPK, with binding enhanced by glucose treatment. Regulation by glucose of phospho-AMPK in hypothalamic cell lines is prevented by blocking AMPK-IPMK binding. These findings imply that IPMK inhibitors will be beneficial in treating obesity and diabetes.

引用

页码：616 / 620

页数：5

共 30 条

[1]

Intrasteric control of AMPK via the γ1 subunit AMP allosteric regulatory site [J].

Adams, J ;

Chen, ZP ;

Van Denderen, BJW ;

Morton, CJ ;

Parker, MW ;

Witters, LA ;

Stapleton, D ;

Kemp, BE .

PROTEIN SCIENCE, 2004, 13 (01) :155-165

[2]

The AMP-activated protein kinase cascade - a unifying system for energy control [J].

Carling, D .

TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (01) :18-24

[3]

Inositol polyphosphate multikinase regulates inositol 1,4,5,6-tetrakisphosphate [J].

Chang, SC ;

Majerus, PW .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 339 (01) :209-216

[4]

Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding [J].

Cheung, PCF ;

Salt, IP ;

Davies, SP ;

Hardie, DG ;

Carling, D .

BIOCHEMICAL JOURNAL, 2000, 346 :659-669

[5]

Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome [J].

Corradetti, MN ;

Inoki, K ;

Bardeesy, N ;

DePinho, RA ;

Guan, KL .

GENES & DEVELOPMENT, 2004, 18 (13) :1533-1538

[6]

Hypothalamic mTOR signaling regulates food intake [J].

Cota, D ;

Proulx, K ;

Smith, KAB ;

Kozma, SC ;

Thomas, G ;

Woods, SC ;

Seeley, RJ .

SCIENCE, 2006, 312 (5775) :927-930

[7]

5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2A(c) [J].

Davies, SP ;

Helps, NR ;

Cohen, PTW ;

Hardie, DG .

FEBS LETTERS, 1995, 377 (03) :421-425

[8]

Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy [J].

Egan, Daniel F. ;

Shackelford, David B. ;

Mihaylova, Maria M. ;

Gelino, Sara ;

Kohnz, Rebecca A. ;

Mair, William ;

Vasquez, Debbie S. ;

Joshi, Aashish ;

Gwinn, Dana M. ;

Taylor, Rebecca ;

Asara, John M. ;

Fitzpatrick, James ;

Dillin, Andrew ;

Viollet, Benoit ;

Kundu, Mondira ;

Hansen, Malene ;

Shaw, Reuben J. .

SCIENCE, 2011, 331 (6016) :456-461

[9]

Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2 [J].

Garami, A ;

Zwartkruis, FJT ;

Nobukuni, T ;

Joaquin, M ;

Roccio, M ;

Stocker, H ;

Kozma, SC ;

Hafen, E ;

Bos, JL ;

Thomas, G .

MOLECULAR CELL, 2003, 11 (06) :1457-1466

[10]

AMPK phosphorylation of raptor mediates a metabolic checkpoint [J].

Gwinn, Dana M. ;

Shackelford, David B. ;

Egan, Daniel F. ;

Mihaylova, Maria M. ;

Mery, Annabelle ;

Vasquez, Debbie S. ;

Turk, Benjamin E. ;

Shaw, Reuben J. .

MOLECULAR CELL, 2008, 30 (02) :214-226

← 1 2 3 →