Sci. STKE, 18 December 2007
Biochemistry PIKing Oncogenic Mutations
Science, AAAS, Washington, DC 20005, USA
Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that can initiate a variety of signaling events. Many human cancers involve mutations that activate PI3K, a heterodimer composed of a catalytic subunit, p110, and a regulatory subunit, p85, both of which contain multiple domains. Huang et al. describe the crystal structure of a complex between the full-length human p110 catalytic subunit and the binding and activation domains of the p85 regulatory subunit. The structure provides insight into how oncogenic mutations affect enzyme activity and could assist in the future design of isoform- or mutation-specific inhibitors.
C.-H. Huang, D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, L. M. Amzel, The structure of a human p110/p85 complex elucidates the effects of oncogenic PI3K mutations. Science 318, 1744-1748 (2007). [Abstract] [Full Text]
Citation: V. Vinson, PIKing Oncogenic Mutations. Sci. STKE 2007, tw457 (2007).
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