Structural comparisons of class I phosphoinositide 3-kinases

被引：87

作者：

Amzel, L. Mario ^{[1
]}

Huang, Chuan-Hsiang ^{[1
,2
]}

Mandelker, Diana ^{[3
,4
]}

Lengauer, Christoph ^{[3
,4
]}

Gabelli, Sandra B. ^{[1
]}

Vogelstein, Bert ^{[3
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD 21205 USA

[3] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA

[4] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA

来源：

NATURE REVIEWS CANCER | 2008年 / 8卷 / 09期

关键词：

D O I：

10.1038/nrc2443

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3K alpha, is frequently mutated in diverse tumour types. The recently determined structure of PI3K alpha reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3K gamma differs from PI3K alpha by a substitution identical to a PI3K alpha oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic activities of the normal and mutant PI3K alpha. Comparison of the PI3K structures also identified structural features that could potentially be exploited for the design of isoform-specific inhibitors.

引用

页码：665 / 669

页数：5

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