Somatic mutations in PI3Kalpha: structural basis for enzyme activation and drug design.

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

Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, MD 21205, USA. gabelli@jhmi.edu

Biochimica et biophysica acta 2010 Mar

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The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kalpha 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. Copyright 2009 Elsevier B.V. All rights reserved.

Citation

Sandra B Gabelli, Diana Mandelker, Oleg Schmidt-Kittler, Bert Vogelstein, L Mario Amzel. Somatic mutations in PI3Kalpha: structural basis for enzyme activation and drug design. Biochimica et biophysica acta. 2010 Mar;1804(3):533-40