Abstract

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

Author affiliations

1. L. Mario Amzel, Chuan-Hsiang Huang and Sandra B. Gabelli are at the Department of Biophysics and Biophysical Chemistry,Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
2. Chuan-Hsiang Huang is at the Graduate Program in Immunology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
3. Diana Mandelker, Christoph Lengauer and Bert Vogelstein are at the Ludwig Center for Cancer Genetics and Therapeutics, and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, 1,650 Orleans Street, Baltimore, Maryland 21231, USA.
4. Christoph Lengauer is currently at the Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
5. L.M.A and C.-H.H. contributed equally to this work.

Correspondence to: Bert Vogelstein³ Email: vogelbe@jhmi.edu

Published online 17 July 2008

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