Receptor tyrosine phosphatases in physiology and disease. (360G-Wellcome-109407_Z_15_Z)
The reversible phosphorylation of tyrosine residues on proteins serves as a critical switch in the regulation of fundamental cellular processes and is controlled by the antagonistic actions of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Dysregulation of this balance is associated with numerous diseases as well as developmental abnormalities. Located at the cell surface, the receptor subfamily of PTPs (RPTPs) have the potential to function as key environmental sensors by me diating important processes such as cell-cell adhesion and intercellular signalling. Moreover, several RPTPs have recently been implicated in physiological functions important for human health, yet the physiological roles, substrates and regulation of many receptors remain elusive. The receptor PTPRK was identified as a candidate tumour suppressor in the mouse intestine by a forward genetics screen. In humans it is mutated in ~10% of colorectal cancers, and is a recurrent gene fusion partner, re sulting in heterozygosity. My goal is to use a multidisciplinary approach to reveal the physiological role of PTPRK, initially in gastrointestinal homeostasis, and to identify regulators and substrates that are key to its function. These advances will reveal new modes of cell signalling through tyrosine dephosphorylation and novel cellular mechanisms that serve to restrain oncogenic kinase signalling.
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Grant Details
Amount Awarded | 1074941 |
Applicant Surname | Sharpe |
Approval Committee | Sir Henry Dale Fellowship Interview Committee |
Award Date | 2015-10-21T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Sir Henry Dale Fellowship |
Internal ID | 109407/Z/15/Z |
Lead Applicant | Dr Hayley Sharpe |
Partnership Name | Royal Society/Wellcome Trust Sir Henry Dale Fellowship |
Partnership Value | 1074941 |
Planned Dates: End Date | 2019-10-01T00:00:00+00:00 |
Planned Dates: Start Date | 2016-04-04T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |
Sponsor(s) | Prof Gillian Griffiths |