PHUPPing the switch on Akt and protein kinase C signaling

被引：146

作者：

Brognard, John ^{[1
]}

Newton, Alexandra C. ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2008年 / 19卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.tem.2008.04.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The Ser/Thr-specific phosphatase PHLPP pleckstrin homology (PH) domain leucine-rich repeat protein phosphatasel provides 'the brakes' for Akt and protein kinase C (PKC) signaling. The two isoforms of this recently discovered family, PHLPP1 and PHLPP2, control the amplitude and duration of signaling of Akt and PKC by catalyzing the dephosphorylation of the hydrophobic phosphorylation motif, a C-terminal phosphorylation switch that controls these kinases. Aberrant regulation of either kinase accompanies many diseases, notably diabetes and cancer. By specifically dephosphorylating the hydrophobic motif, PHLPP controls the degree of agonist-evoked signaling by Akt and the cellular levels of PKC. This review focuses on the function of PHLPP1 and PHLPP2 in modulating signaling by Akt and PKC.

引用

页码：223 / 230

页数：8

共 64 条

[1] Mechanism of activation of protein kinase B by insulin and IGF-1 [J].

Alessi, DR ;

Andjelkovic, M ;

Caudwell, B ;

Cron, P ;

Morrice, N ;

Cohen, P ;

Hemmings, BA .

EMBO JOURNAL, 1996, 15 (23) :6541-6551

[2] Oncogenic kinase signalling [J].

Blume-Jensen, P ;

Hunter, T .

NATURE, 2001, 411 (6835) :355-365

[3] Ten years of protein kinase B signalling: a hard Akt to follow [J].

Brazil, DP ;

Hemmings, BA .

TRENDS IN BIOCHEMICAL SCIENCES, 2001, 26 (11) :657-664

[4] PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms [J].

Brognard, John ;

Sierecki, Emma ;

Gao, Tianyan ;

Newton, Alexandra C. .

MOLECULAR CELL, 2007, 25 (06) :917-931

[5] Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor [J].

Brunet, A ;

Bonni, A ;

Zigmond, MJ ;

Lin, MZ ;

Juo, P ;

Hu, LS ;

Anderson, MJ ;

Arden, KC ;

Blenis, J ;

Greenberg, ME .

CELL, 1999, 96 (06) :857-868

[6] Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo [J].

Calleja, Veronique ;

Alcor, Damien ;

Laguerre, Michel ;

Park, Jongsun ;

Vojnovic, Borivoj ;

Hemmings, Brian A. ;

Downward, Julian ;

Parker, Peter J. ;

Larijani, Banafshe .

PLOS BIOLOGY, 2007, 5 (04) :780-791

[7] The phosphoinositide 3-kinase pathway [J].

Cantley, LC .

SCIENCE, 2002, 296 (5573) :1655-1657

[8] A transforming mutation in the pleckstrin homology domain of AKT1 in cancer [J].

Carpten, John D. ;

Faber, Andrew L. ;

Horn, Candice ;

Donoho, Gregory P. ;

Briggs, Stephen L. ;

Robbins, Christiane M. ;

Hostetter, Galen ;

Boguslawski, Sophie ;

Moses, Tracy Y. ;

Savage, Stephanie ;

Uhlik, Mark ;

Lin, Aimin ;

Du, Jian ;

Qian, Yue-Wei ;

Zeckner, Douglas J. ;

Tucker-Kellogg, Greg ;

Touchman, Jeffrey ;

Patel, Ketan ;

Mousses, Spyro ;

Bittner, Michael ;

Schevitz, Richard ;

Lai, Mei-Huei T. ;

Blanchard, Kerry L. ;

Thomas, James E. .

NATURE, 2007, 448 (7152) :439-U1

[9]

Cohen PTW, 2004, TOP CURR GENET, V5, P1

[10] Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients [J].

Cozzone, D. ;

Froejdoe, S. ;

Disse, E. ;

Debard, C. ;

Laville, M. ;

Pirola, L. ;

Vidal, H. .

DIABETOLOGIA, 2008, 51 (03) :512-521

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