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DFG project G:(GEPRIS)124046702
Protein tryrosine phosphatase and glucocorticoids as modulators of mast cell action
| Coordinator | Professor Dr. Andrew C.B. Cato |
| Grant period | 2009 - 2017 |
| Funding body | Deutsche Forschungsgemeinschaft |
| DFG | |
| Identifier | G:(GEPRIS)124046702 |
⇧ SPP 1394: Mast-cells - promoters of health and modulators of disease ⇧
Note: Protein tyrosine phosphatases play important role in immune function. They dephosphorylate and inactivate signals emanating from the plasma membrane to influence different processes within cells. In allergic reactions, signals triggered at the surface of mast cells are also inactivated by protein tyrosine phosphatases (PTP). As several PTPs are transcriptionally regulated by glucocorticoids, it is thought that the anti-allergic effects of glucocorticoids occur through the regulation of expression of these genes. The long-term application of glucocorticoid is however associated with several adverse reactions, requiring a better understanding of its mode of action for the development of alternative therapeutic strategies for allergy. The aim of this work is to use knock-out mouse models and biochemical and molecular biological techniques to determine whether glucocorticoid-mediated regulation of PTPs contribute to anti-allergic reactions. We will further develop our previously finding that PEST-domain-enriched tyrosine phosphatase (PEP), one of the PTPs upregulated by glucocorticoids, is a positive regulator of anaphylaxis. We will build upon this important finding to identify the mechanism of action of PEP in mast cells and to characterize a series of novel chemical probes of PEP that together with glucocorticoids could serve as potent inhibitors of mouse and human mast cell action. It is hoped that these studies will greatly increase our understanding on activation mechanisms in mast cells and will pave the way to the search for more effective compounds for anti-allergic therapy.