PP2A Regulatory Subunit PP2A-B′ Counteracts S6K Phosphorylation

被引：108

作者：

Hahn, Katrin ^{[1
]}

Miranda, Merce ^{[2
,3
]}

Francis, Victor A. ^{[1
,2
,4
,5
]}

Vendrell, Joan ^{[2
,3
]}

Zorzano, Antonio ^{[2
,4
,5
]}

Teleman, Aurelio A. ^{[1
]}

机构：

[1] German Canc Res Ctr, D-69120 Heidelberg, Germany

[2] CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona 08036, Spain

[3] Univ Rovira & Virgili, Endocrinol & Diabet Unit, Res Dept, Univ Hosp Tarragona Joan XXIII,Pere Virgili Inst, Tarragona 43007, Spain

[4] IRB Barcelona, Barcelona 08028, Spain

[5] Univ Barcelona, Dept Bioquim & Biol Mol, Fac Biol, E-08028 Barcelona, Spain

来源：

CELL METABOLISM | 2010年 / 11卷 / 05期

关键词：

INSULIN; DROSOPHILA; GROWTH; SIZE; HOMEOSTASIS; DOWNSTREAM; KINASE; MTOR; GENE;

D O I：

10.1016/j.cmet.2010.03.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The insulin/TOR signaling pathway plays a crucial role in animal homeostasis, sensing nutrient status to regulate organismal growth and metabolism. We identify here the Drosophila B' regulatory subunit of PP2A (PP2A-B') as a novel, conserved component of the insulin pathway that specifically targets the PP2A holoenzyme to dephosphorylate S6K. PP2A-B' knockout flies have elevated S6K phosphorylation and exhibit phenotypes typical of elevated insulin signaling such as reduced total body triglycerides and reduced longevity. We show that PP2A-B' interacts with S6K both physically and genetically. The human homolog of PP2A-B', PPP2R5C, also counteracts S6K1 phosphorylation, indicating a conserved mechanism in mammals. Since S6K affects development of cancer and metabolic disease, our data identify PPP2R5C as a novel factor of potential medical relevance.

引用

页码：438 / 444

页数：7

共 30 条

[21] A PP2A Regulatory Subunit Regulates C-elegans Insulin/IGF-1 Signaling by Modulating AKT-1 Phosphorylation [J].