Structural comparisons of class I phosphoinositide 3-kinases

L. Mario Amzel; Chuan Hsiang Huang; Diana Mandelker; Christoph Lengauer; Sandra B. Gabelli; Bert Vogelstein

doi:10.1038/nrc2443

Structural comparisons of class I phosphoinositide 3-kinases

L. Mario Amzel, Chuan Hsiang Huang, Diana Mandelker, Christoph Lengauer, Sandra B. Gabelli, Bert Vogelstein

Research output: Contribution to journal › Review article › peer-review

74 Scopus citations

Abstract

Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3Kα, is frequently mutated in diverse tumour types. The recently determined structure of PI3Kα reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3Kγ differs from PI3Kα by a substitution identical to a PI3Kα oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic activities of the normal and mutant PI3Kα. Comparison of the PI3K structures also identified structural features that could potentially be exploited for the design of isoform-specific inhibitors.

Original language	English (US)
Pages (from-to)	665-669
Number of pages	5
Journal	Nature Reviews Cancer
Volume	8
Issue number	9
DOIs	https://doi.org/10.1038/nrc2443
State	Published - Sep 2008

ASJC Scopus subject areas

Oncology
Cancer Research

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abstract = "Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3Kα, is frequently mutated in diverse tumour types. The recently determined structure of PI3Kα reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3Kγ differs from PI3Kα by a substitution identical to a PI3Kα oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic activities of the normal and mutant PI3Kα. Comparison of the PI3K structures also identified structural features that could potentially be exploited for the design of isoform-specific inhibitors.",

author = "Amzel, {L. Mario} and Huang, {Chuan Hsiang} and Diana Mandelker and Christoph Lengauer and Gabelli, {Sandra B.} and Bert Vogelstein",

note = "Funding Information: Support was provided by the Virginia and D. K. Ludwig Fund for Cancer Research, NIH grants CA43460 to B.V., GM066895 to L.M.A, and GM07309 and GM07184 to D.M.",

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AU - Huang, Chuan Hsiang

AU - Mandelker, Diana

AU - Lengauer, Christoph

AU - Gabelli, Sandra B.

AU - Vogelstein, Bert

N1 - Funding Information: Support was provided by the Virginia and D. K. Ludwig Fund for Cancer Research, NIH grants CA43460 to B.V., GM066895 to L.M.A, and GM07309 and GM07184 to D.M.

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AB - Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3Kα, is frequently mutated in diverse tumour types. The recently determined structure of PI3Kα reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3Kγ differs from PI3Kα by a substitution identical to a PI3Kα oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic activities of the normal and mutant PI3Kα. Comparison of the PI3K structures also identified structural features that could potentially be exploited for the design of isoform-specific inhibitors.

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Structural comparisons of class I phosphoinositide 3-kinases

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