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The molecular mechanisms which underlie the role of phosphoinositide 3-kinase (PI3K) and the monomeric GTPase rac as an intracellular signalling cassette

Reference	ICR07551
Principal Investigator / Supervisor	Professor Len Stephens
Co-Investigators / Co-Supervisors	Dr Phillip Hawkins
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	138,480
Status	Completed
Type	Research Grant
Start date	29/10/1997
End date	29/10/2000
Duration	36 months

Abstract

We intend to use a number of independent strategies to identify the proteins and molecular mechanisms that are involved in the processes by which PI3K and its lipid products stimulate activation of the monomeric GTPase rac and hence a diverse range of cellular responses. We shall utilise two model systems; FMLP-stimulated, PI3K and rac-dependent, activation of superoxide production in neutrophils and PDGF- stimulated, PI3K and rac-dependent rearrangements in the filamentous actin cytoskeleton in endothelial cells. In both situations N17 rac can act as a dominant negative inhibitor, we plan to use this fact and to use epitope-tagged N17 rac to purify the guanine nucleotide exchange factor(s) responsible for mediating these effects of PI3K and to attempt to reconstitute signalling using synthetically-derived enantiomerically-resolved, D and L PtdIns3P, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. We shall also attempt to identify novel genes involved in the latter system by isolating cells carrying loss of function mutations blocking PI3K-dependent activation of rac.

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	Integration of Cellular Responses (ICR) [1996]
Funding Scheme	X – not Funded via a specific Funding Scheme

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