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Sci. STKE, 17 July 2007
Vol. 2007, Issue 395, p. tw255
[DOI: 10.1126/stke.3952007tw255]

EDITORS' CHOICE

Structural Biology Crystallized Kinase Regulation

Valda Vinson

Science, AAAS, Washington, DC 20005, USA

Many human cancers involve gain-of-function mutations in the phosphoinositide 3-kinase PI3K{alpha}. The kinase is a heterodimer of a catalytic subunit (p110{alpha}) and a regulatory subunit (p85{alpha}), with both subunits comprising multiple domains. Miled et al. (see the Perspective by Lee et al.) have determined the crystal structure of the adaptor binding domain of p110{alpha} bound to the inter-SH2 domain of p85{alpha} at 2.4 angstrom resolution and have performed functional studies to investigate the effect of oncogenic mutations in the helical domain of p110{alpha} on its interaction with the N-terminal SH2 domain of p85{alpha}. The studies suggest how these two classes of mutations cause the up-regulation of PI3K{alpha} that can lead to cancer.

N. Miled, Y. Yan, W.-C. Hon, O. Perisic, M. Zvelebil, Y. Inbar, D. Schneidman-Duhovny, H. J. Wolfson, J. M. Backer, R. L. Williams, Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science 317, 239-242 (2007). [Abstract] [Full Text]

J. Y. Lee, J. A. Engelman, L. C. Cantley, PI3K charges ahead. Science 317, 206-207 (2007). [Summary] [Full Text]

Citation: V. Vinson, Crystallized Kinase Regulation. Sci. STKE 2007, tw255 (2007).

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