Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis

被引：189

作者：

Banko, Max R. ^{[1
]}

Allen, Jasmina J. ^{[3
,4
]}

Schaffer, Bethany E. ^{[1
,2
]}

Wilker, Erik W. ^{[5
]}

Tsou, Peiling ^{[6
,8
]}

White, Jamie L. ^{[1
]}

Villen, Judit ^{[7
]}

Wang, Beatrice ^{[3
,4
]}

Kim, Sara R. ^{[5
]}

Sakamoto, Kei ^{[9
]}

Gygi, Steven P. ^{[7
]}

Cantley, Lewis C. ^{[6
,8
]}

Yaffe, Michael B. ^{[5
]}

Shokat, Kevan M. ^{[3
,4
]}

Brunet, Anne ^{[1
,2
]}

机构：

[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[2] Stanford Univ, Canc Biol Grad Program, Stanford, CA 94305 USA

[3] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA

[5] MIT, Dept Biol & Biol Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[6] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[8] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

[9] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland

来源：

MOLECULAR CELL | 2011年 / 44卷 / 06期

基金：

美国国家卫生研究院;

关键词：

POLO-LIKE KINASE; LIGHT-CHAIN PHOSPHORYLATION; MYOSIN PHOSPHATASE; METABOLIC CHECKPOINT; GLUCOSE-HOMEOSTASIS; MITOTIC APPARATUS; TUMOR-SUPPRESSOR; ACTIVE FORM; C-ELEGANS; LIFE-SPAN;

D O I：

10.1016/j.molcel.2011.11.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.

引用

页码：878 / 892

页数：15

共 57 条

[1] Chemical genetic approaches for the elucidation of signaling pathways [J].