Regulation of TNF and SFK signalling in immune cells by TCPTP

Funded Activity Summary

Tumour necrosis factor (TNF) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation. TNF acts on the cell surface to activate two key cellular communication or signalling pathways: the mitogen-activated protein kinase (MAPK) pathway and the nuclear factor kappaB (NFkappaB) pathway. The relative activation of the two pathways can dictate whether cells live and proliferate or differentiate or otherwise die in response to TNF, and therefore determine the nature of the immune or inflammatory response. The T-cell protein tyrosine phosphatase (TCPTP) is known to be important in the immune system and serves as a negative regulator of inflammation. Our preliminary studies have identified TCPTP as a selective regulator of TNF-induced MAPK but not NFkappaB signaling. TCPTP exerts its effects by inactivating Src family kinases (SFK) which are themselves integral to immune and inflammatory responses. In this proposal we will elucidate the molecular basis for TCPTP function in TNF- signalling and characterise the role of TCPTP in TNF and SFK functions in immune cells, in particular T-cells.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $454,023.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Immunology

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Src family tyrosine kinases | T lymphocyte response | T lymphocytes | Tumour necrosis factor (TNF) | cell signalling | immune response | inflammation | protein tyrosine phosphatase | signal transduction

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