Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535597
Title: Partnerships and phosphorylation of cyclic AMP phosphodiesterase-4A5
Author: MacKenzie, Kirsty Faye
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2011
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Abstract:
Phosphodiesterase 4 enzymes hydrolyse the second messenger cyclic AMP and therefore are set to play an important role in cell signaling. In this thesis I investigate the phosphorylation and protein-protein interactions of the cAMP hydrolyzing phosphodiesterase isoform, PDE4A4/5. In the first of my studies I show that PDE4A4/5 can be phosphorylated by MAPKAPK2 (MK2) the downstream kinase of the p38 MAPK signalling pathway. This phosphorylation reaction attenuates the degree of activation of PDE4A5 elicited through phosphorylation by Protein Kinase A. I also show that MAPKAPK2 can bind directly to PDE4A4/5 and map the two binding sites required by peptide array technology. In the second of my studies I show that PDE4A4/5 interacts with the low affinity neurotrophin receptor, p75NTR. This interaction inhibits normal fibrin breakdown in an in vitro model. I also show that phosphorylation of PDE4A5 by MAPKAPK2 enhances the inhibition of fibrin breakdown and increases PDE4A5:p75NTR complex formation. In the final study described in this thesis I show that long form PDE4 isoforms contain a potential multi-functional docking site where several partner proteins are able to bind. In conclusion, the work described in this thesis provides a valuable insight into PDE4A4/5, its interacting proteins, phosphorylation status and the potential for exploitation of this novel information therapeutically.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.535597  DOI: Not available
Keywords: Q Science (General)
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