Somatic mutations in PI3Kα: Structural basis for enzyme activation and drug design

Sandra B. Gabelli; Diana Mandelker; Oleg Schmidt-Kittler; Bert Vogelstein; L. Mario Amzel

doi:10.1016/j.bbapap.2009.11.020

Somatic mutations in PI3Kα: Structural basis for enzyme activation and drug design

Sandra B. Gabelli, Diana Mandelker, Oleg Schmidt-Kittler, Bert Vogelstein, L. Mario Amzel

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

11 Scopus citations

Abstract

The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kα harbors recurrent somatic mutations resulting in gains of function in human cancers, it has emerged as an important drug target for many types of solid tumors. Various PI3K isoforms are also being evaluated as potential therapeutic targets for inflammation, heart disease, and hematological malignancies. Structural biology is providing insights into the flexibility of the PI3Ks, and providing basis for understanding the effects of mutations, drug resistance and specificity.

Original language	English (US)
Pages (from-to)	533-540
Number of pages	8
Journal	Biochimica et Biophysica Acta - Proteins and Proteomics
Volume	1804
Issue number	3
DOIs	https://doi.org/10.1016/j.bbapap.2009.11.020
State	Published - Mar 2010
Externally published	Yes

Keywords

Gain of function
H1047R mutant
PI3K
Somatic mutation
p110/p85

ASJC Scopus subject areas

Analytical Chemistry
Biophysics
Biochemistry
Molecular Biology

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10.1016/j.bbapap.2009.11.020

Cite this

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title = "Somatic mutations in PI3Kα: Structural basis for enzyme activation and drug design",

abstract = "The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kα harbors recurrent somatic mutations resulting in gains of function in human cancers, it has emerged as an important drug target for many types of solid tumors. Various PI3K isoforms are also being evaluated as potential therapeutic targets for inflammation, heart disease, and hematological malignancies. Structural biology is providing insights into the flexibility of the PI3Ks, and providing basis for understanding the effects of mutations, drug resistance and specificity.",

keywords = "Gain of function, H1047R mutant, PI3K, Somatic mutation, p110/p85",

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note = "Funding Information: Support was provided by the Virginia and D.K. Ludwig Fund for Center Research and National Institutes of Health Grants CA43460 , GM07309 , and GM07184 .",

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AU - Gabelli, Sandra B.

AU - Mandelker, Diana

AU - Schmidt-Kittler, Oleg

AU - Vogelstein, Bert

AU - Amzel, L. Mario

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AB - The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kα harbors recurrent somatic mutations resulting in gains of function in human cancers, it has emerged as an important drug target for many types of solid tumors. Various PI3K isoforms are also being evaluated as potential therapeutic targets for inflammation, heart disease, and hematological malignancies. Structural biology is providing insights into the flexibility of the PI3Ks, and providing basis for understanding the effects of mutations, drug resistance and specificity.

KW - Gain of function

KW - H1047R mutant

KW - PI3K

KW - Somatic mutation

KW - p110/p85

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Somatic mutations in PI3Kα: Structural basis for enzyme activation and drug design

Abstract

Keywords

ASJC Scopus subject areas

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