Lipid Kinases

PI3 kinases are at the heart of one of the major pathways of intracellular signal transduction. The signals made by these enzymes influence a wide variety of cellular functions, including cell growth, differentiation and survival, glucose metabolism and cytoskeletal organization.

Dysregulation of the PI3 kinase signaling cascades can lead to cancer. Many steps in the PI3 kinase signalling pathway are mutated, hyperactivated or over expressed in human cancers.

As targets for drug development, lipid kinases have lagged behind the protein kinases, but this trend may be set to change. Three recent studies identifying specific and parallel functions of lipid kinases may open the door to the development of drugs targeting specific phosphoinositide-3'-OH kinase (PI3-K) family members. Knight et al. (2006) report a detailed pharmacological analysis of PI3-K isoforms using small molecule inhibitors. In addition, recent publications in Nature (Foukas et al., 2006) and Cancer Cell (Fan et al., 2006) describe advances in understanding PI3-K function and in the development of treatments based on the selective inhibition of PI3-K isoforms.

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Related Links

Poster on "Expression and Purification of PI3 kinase alpha and Development of a Luminometric PI3 Kinase Activity Assay" presented by KinaseDetect at Screening Europe 2008 in Stockholm, Sweden.

Angiogenesis selectively requires the p110a isoform of PI3K to conrol endothelial migration

PI3 Kinases in Cancer: From oncogene artifact to leading cancer target

PI3K inhibitors in cardiovascular disease

Advances in development of phosphatidylinositol 3-kinase inhibitors

Insights into the oncogenic effects of PIK3CA mutations from the structure of p110alpha/p85alpha