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The Molecular mechanisms by which PtdIns(3,4,5)P3, PtdIns (3,4)P2 and PtdIns3P signals are transduced

Reference	BBS/E/B/0000L391
Principal Investigator / Supervisor	Dr Phillip Hawkins
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	99,243
Status	Completed
Type	Institute Project
Start date	01/10/1998
End date	30/09/2003
Duration	60 months

Abstract

The role of PI3Ks and their lipid products in intracellular signalling are now more widely established. It is believed that PtdIns(3,4,5)P3 and PtdIns(3,4)P2 might act as signals for recruitment of specific proteins to precise intracellular locations. The main focus of the work in this project will investigate two cellular responses using the PI3K pathways. (1) PtdIns(3,4,5)P3 activation of superoxide formation in a neutrophil derived cell-free systems and (2) PtdIns(3,4,5)P3 and PtdIns (3,4)P2 regulated activation of phosphorylation of the cellular targets of PKB kinases and PKB. Neutrophils can produce large quantities of bacteriocidal superoxide ions when appropriately activated. We are purifying factors from neutrophil cytosol which confer the ability of PtdIns(3,4,5)P3 to activate superoxide formation in a recombinant assay and will use these to examine the mechanism by which superoxide formation is regulated. This system will act as a model for understanding other responses using the same pathway. We will also investigate other potential substrates for the PKB kinase we have characterised. This will involve co-transfection of COS and PAE cells with an activated allele of PKB kinase and potential candidates. Examination of immunoprecipitates for labelled molecules will indicate which of the target molecules are substrates for PKB.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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