The role of plasma membrane microdomains in regulating Ras-dependent Raf activation

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/210164

Funding Status
Closed

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Funded Activity Summary

In human cancers one or more of the signaling pathways leading from growth factor receptors at the cell surface to the nucleus where cell division is initiated are subverted. For example, a protein called Ras, that regulates a series of major signaling pathways, is mutated in 25% of all human tumours. This leaves Ras and the signaling pathways permanently switched on causing uncontrolled cell proliferation. Our previous work has demonstrated that Ras must be attached to the inner surface of the cell membrane in order to function properly. This project now seeks to understand exactly how Ras attaches to and interacts with specific sites in the plasma membrane. Its is becoming clear that different isoforms of Ras, called H-, N- and K-ras have different functions in the cell which may in turn result from their different sites of attachment to the cell membrane. This is important because by understanding the precise micro-environment in which the different Ras proteins operate and how they activate subsequent proteins in their signaling networks we will be in a good position to design drugs that selectively compromise the function of each specific Ras isoform. A highly relevant example is provided by K-ras which is mutated in 90% of all pancreatic cancers and 50% of all colon cancers. Clearly the clinical impact of a drug that could selectively neutralise K-Ras function in these tumours is potentially enormous.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $216,100.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Protein Targeting And Signal Transduction

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Acute leukaemia | Cancer biology | Colon cancer | Lipid Rafts | Plasma membrane microdomains | Raf-1 activation | Ras signalling

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