Phosphoinositide 3-kinase: From viral oncoprotein to drug target

被引：34

作者：

Vogt, PK ^{[1
]}

Bader, AG ^{[1
]}

Kang, S ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

来源：

VIROLOGY | 2006年 / 344卷 / 01期

关键词：

D O I：

10.1016/j.virol.2005.09.027

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The catalytic subunit p110 alpha of the phosphomositide 3-kinase (PI3K) and the serine-threonine protein kinase Akt have been extensively studied as retroviral oncoproteins. The experimental tools developed with the retroviral vectors are now being applied to PI3K mutations in human cancer. The most frequently occurring mutants of p110 alpha are oncogenic in vitro and in vivo, show gain of enzymatic function, activate Akt, and their oncogenic activity is sensitive to rapamycin. The related isoforms p110 beta, gamma and delta induce oncogenic transformation as wild-type proteins. Mutated p110 alpha proteins are ideal drug targets. Identification of small molecule inhibitors that specifically target these mutant proteins is a realistic and urgent goal. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：131 / 138

页数：8

共 105 条

[1] Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha
Alessi, DR
James, SR
Downes, CP
Holmes, AB
Gaffney, PRJ
Reese, CB
Cohen, P
[J]. CURRENT BIOLOGY, 1997, 7 (04) : 261 - 269
[2] Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity
Ali, IU
Schriml, LM
Dean, M
[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (22): : 1922 - 1932
[3] Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B
Anderson, KE
Coadwell, J
Stephens, LR
Hawkins, PT
[J]. CURRENT BIOLOGY, 1998, 8 (12) : 684 - 691
[4] Role of translocation in the activation and function of protein kinase B
Andjelkovic, M
Alessi, DR
Meier, R
Fernandez, A
Lamb, NJC
Frech, M
Cron, P
Cohen, P
Lucocq, JM
Hemmings, BA
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (50) : 31515 - 31524
[5] The Akt kinase:: Molecular determinants of oncogenicity
Aoki, M
Batista, O
Bellacosa, A
Tsichlis, P
Vogt, PK
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) : 14950 - 14955
[6] A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt
Aoki, M
Blazek, E
Vogt, PK
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (01) : 136 - 141
[7] The catalytic subunit of phosphoinositide 3-kinase: Requirements for oncogenicity
Aoki, M
Schetter, C
Himly, M
Batista, O
Chang, HW
Vogt, PK
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (09) : 6267 - 6275
[8] The PIK3CA gene is mutated with high frequency in human breast cancers
Bachman, KE
Argani, P
Samuels, Y
Silliman, N
Ptak, J
Szabo, S
Konishi, H
Karakas, B
Blair, BG
Lin, C
Peters, BA
Velculescu, VE
Park, BH
[J]. CANCER BIOLOGY & THERAPY, 2004, 3 (08) : 772 - 775
[9] AKT2 is frequently upregulated in HER-2/neu-positive breast cancers and may contribute to tumor aggressiveness by enhancing cell survival
Bacus, SS
Altomare, DA
Lyass, L
Chin, DM
Farrell, MP
Gurova, K
Gudkov, A
Testa, JR
[J]. ONCOGENE, 2002, 21 (22) : 3532 - 3540
[10] Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway
Bader, AG
Feits, KA
Jiang, N
Chang, HW
Vogt, PK
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (21) : 12384 - 12389

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