title: Synergy in activating class I PI3Ks.
abstract: The class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that transduce a host of cellular signals and regulate a broad range of essential functions including growth, proliferation, and migration. As such, PI3Ks have pivotal roles in diseases such as cancer, diabetes, primary immune disorders, and inflammation. These enzymes are activated downstream of numerous activating stimuli including receptor tyrosine kinases, G protein-coupled receptors (GPCRs), and the Ras superfamily of small G proteins. A major challenge is to decipher how each PI3K isoform is able to successfully synergize these inputs into their intended signaling function. This article highlights recent progress in characterizing the molecular mechanisms of PI3K isoform-specific activation pathways, as well as novel roles for PI3Ks in human diseases, specifically cancer and immune diseases.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, 3800 Finnerty Drive, Victoria BC, V8P 5C2, Canada. Electronic address: jeburke@uvic.ca.
authors.forename: John E
authors.initials: JE
authors.lastname: Burke
authors.affiliation: Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0QH, UK.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D006801:Humans; D007154:Immune System Diseases / Q000201:enzymology* / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D010716:Phosphatidylinositols; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D010716:Phosphatidylinositols; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases
keywords: cancer; lipid kinases; lipid signaling; phosphoinositide 3 kinases; phosphoinositides; primary immunodeficiencies