Cel Many signaling pathways in human cells involve lipid recognition events. The phosphorylation state of these lipids is under the control of both lipid kinases and lipid phosphatases. The phosphorylated second messenger lipids recruit lipid adaptor molecules, which regulate fundamental cellular processes including cell survival, proliferation, motility, differentiation and intracellular trafficking. Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate the 3’ hydroxyl group of inositol phosphate. The class IA PI3K family is associated with diseases including cancer, thrombosis, allergies and arthritis. Although it is clear that these PI3Ks are activated by Receptor Tyrosine Kinases (RTKs), PI3Kβ is the single member of the PI3Ks that is activated downstream of both RTKs and G-protein coupled receptors (GPCRs).Using a combination of X-ray crystallography, in vitro activity assays and cellular experiments, I want to characterise the mechanisms specific to PI3Kß regulation. A first step will consist in the determination of PI3Kß structures in complex with G-protein ßγ heterodimers and with the small GTPase Rab5. That structural information will serve as an invaluable framework for further design of in vitro and cellular experiments to interrogate the exclusive mechanism of PI3Kβ regulation.Because of the potential role of PI3Kβ in oncogenesis and thrombosis, I will also determine the structures of PI3Kß in complexes with a panel of PI3K isoform-specific inhibitors. These structures will provide the basis for the next generation of therapeutics.This project will weave threads of structural, biophysical, biochemical and cell biology into a tapestry that depicts the roles of this unique enzyme that stands at the cross-road of RTK and GPCR signalling. Dziedzina nauki medical and health sciencesclinical medicinerheumatologymedical and health sciencesclinical medicineangiologyvascular diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicineallergology Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Zaproszenie do składania wniosków FP7-PEOPLE-2010-IEF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IEF - Intra-European Fellowships (IEF) Koordynator MEDICAL RESEARCH COUNCIL Wkład UE € 209 092,80 Adres 20 Park Crescent W1B 1AL LONDON Zjednoczone Królestwo Zobacz na mapie Rodzaj działalności Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Kontakt administracyjny Elizabeth Cutler (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
