Sci. STKE, 17 July 2007
Structural Biology Crystallized Kinase Regulation
Science, AAAS, Washington, DC 20005, USA
Many human cancers involve gain-of-function mutations in the phosphoinositide 3-kinase PI3K. The kinase is a heterodimer of a catalytic subunit (p110) and a regulatory subunit (p85), 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 bound to the inter-SH2 domain of p85 at 2.4 angstrom resolution and have performed functional studies to investigate the effect of oncogenic mutations in the helical domain of p110 on its interaction with the N-terminal SH2 domain of p85. The studies suggest how these two classes of mutations cause the up-regulation of PI3K 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]
Citation: V. Vinson, Crystallized Kinase Regulation. Sci. STKE 2007, tw255 (2007).
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