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Spatial/temporal organisation and regulation of the mapk pathway (MAPK SIGNALLING)

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Proteome map for MAPK cell division pathway

Raf-1 is an important protein in the MAPK pathway, a molecular cascade frequently involved in the cell cycle. Researchers have identified and studied Raf-1 complexes formed by this molecule on its journey through this pathway.

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The MAPK pathway is a means by which many cells promote the start of cell division. It fulfills this function by coupling responses within the cell to the binding of growth factors to cell surface receptors. The pathway is extremely complex and involves many proteins. Its importance in research includes cancer and many immunological disorders when the cascade becomes deregulated in some way. Partners of MAPK SIGNALLING, an EC-funded project, focused their research on one protein in particular, Raf-1. In order to isolate and characterise Raf-1 signalling complexes, researchers at Beatson Institute for Cancer Research used mass spectrometry to identify the components of the complexes formed during the cascade. Three strategies were used to identify important Raf-1 complexes during the execution of this molecular cascade. First, the products of the pathway were compared with those formed by mutants of Raf-1. Secondly, the conditions for the MAPK pathway were varied, an example being serum starvation. Interestingly, this uncovered a molecule that can induce apoptosis or programmed cell death in response to stress signals. Lastly, the isolation of Raf-1 complexes in different subcellular compartments yielded the identification of at least five Raf-1 complexes. Identification of the myriad of protein complexes in the MAPK pathway could well be a major gateway to the identification of protein targets for therapy for cancer and other syndromes linked directly or indirectly to the cell cycle. The unravelling of the complex nature of the MAPK pathway can also lead to identification of side effects of such therapies. Project partners are interested in further collaboration and have already cooperated with other related research projects associated with the MAPK pathway.

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