Abstract
Over the past two decades, our understanding of phospoinositide 3-kinases (PI3Ks) has progressed from the identification of an enzymatic activity associated with growth factors, GPCRs and certain oncogene products to a disease target in cancer and inflammation, with PI3K inhibitors currently in clinical trials. Elucidation of PI3K-dependent networks led to the discovery of the phosphoinositide-binding PH, PX and FYVE domains as conduits of intracellular lipid signalling, the determination of the molecular function of the tumour suppressor PTEN and the identification of AKT and mTOR protein kinases as key regulators of cell growth. Here we look back at the main discoveries that shaped the PI3K field.
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Acknowledgements
Work in the laboratory of B.V. is supported by Cancer Research UK (C23338/A10200) and the UK Biotechnology and Biological Sciences Research Council (BBSRC) (BB/I007806/1). Work in the L.S. and P.H. laboratory is supported by the Welcome Trust (WT 085,889) and the BBSRC (BB/I008489/1, BBI003916/1). The authors apologize to those authors whose work is not cited owing to space constraints or oversight on the authors' part.
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Bart Vanhaesebroeck is a consultant to GSK (Stevenage, UK) and Activiomics (London).
Len Stephens and Phillip Hawkins declare no competing financial interests.
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Vanhaesebroeck, B., Stephens, L. & Hawkins, P. PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol 13, 195–203 (2012). https://doi.org/10.1038/nrm3290
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DOI: https://doi.org/10.1038/nrm3290
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