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Engineering the yeast Slt2p stress-activated MAP kinase for constitutive activity and Hsp90 chaperone independence

Reference	BB/C506721/1
Principal Investigator / Supervisor	Professor Peter William Piper
Co-Investigators / Co-Supervisors
Institution	University of Sheffield
Department	Molecular Biology and Biotechnology
Funding type	Research
Value (£)	205,181
Status	Completed
Type	Research Grant
Start date	01/10/2004
End date	30/09/2007
Duration	36 months

Abstract

The Hsp90 molecular chaperone is essential for the activation of many of the cell¿s most important regulatory proteins. Our understanding of its function has improved greatly over the past few years, but still the means by which the ATPase-driven Hsp90 chaperone cycle is coupled to the activation of client proteins is unclear. Part of Hsp90¿s function may be to promote protein-protein associations that would not otherwise form in vivo. For no protein do we know the detailed molecular changes induced by Hsp90. Sometimes two proteins of almost identical structures are either Hsp90-requiring or Hsp90-independent. This project will study one such instance, an Hsp90-dependent enzyme of the mitogen activated protein (MAP) kinase family (slt2p(mpk1p)) that is structurally almost identical to several other, 40-50 per cent similar MAP kinases that do not require Hsp90 for their activity. Using powerful methods of yeast genetics, especially an adaptation to the two hybrid system that we have developed that enables the monitoring of stress-induced protein-protein interaction in cells, we will attempt to engineer activating mutations and Hsp90-independence into this Slt2p kinase. We will then use bioinformatics to model how these mutations are affecting Slt2p MAP kinase structure, dimerisation, kinase activity and autophosphoylation.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
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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