PDE4 cAMP phosphodiesterases: intracellular targeting and regulation by phosphorylation.

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

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Publications

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Abrahamsen H (2004) TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. in Journal of immunology (Baltimore, Md. : 1950)

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Day JP (2005) Cyclic nucleotide phosphodiesterases in Drosophila melanogaster. in The Biochemical journal

 
Description MRC Capacity Building Studentship
Amount £58,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2007 
End 09/2009
 
Description MRC Programme Grant
Amount £1,900,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2007 
End 09/2011
 
Description Transatlantic Network of Excellence (co-PI)
Amount £500,000 (GBP)
Organisation Transatlantic Networks of Excellence in Cardiovascular Research Program 
Sector Academic/University
Country France
Start 10/2006 
End 09/2011
 
Title Dominant Negative PDE4 constructs 
Description A single point mutation in the active site was first made to catalytically inactive a particular PDE4 isoform. Overexpression of this in cells would 'replace' the tethered cognate form at a particular site in a cell, thereby increasing localized cAMP levels around this specific site, with a defined phenotypic output. This, effectively, inhibits a specific isoform at a specific site. 
Type Of Material Technology assay or reagent 
Year Produced 2006 
Provided To Others? Yes  
Impact We used these novel reagents to great effect in altering people's perception of the functioning of PDE4 isoforms by showing that (i) the tethering of specific isoforms was critical to phenotypic function and that (ii) isoforms had non-redundant roles in cells that depended upon their targeting. Provides proof of principal of a novel therapeutic approach based upon displacing specific PDE4 isoforms from specific sites in cells with much reduced side effects. Extremely beneficial collaborations resulted from sharing these that have greatly aided our research. 
 
Title PDE4 antisera 
Description Antisera specific for each of the four PDE4 sub-families 
Type Of Material Antibody 
Year Produced 2006 
Provided To Others? Yes  
Impact Extremely beneficial collaborations that have greatly aided our research. 
 
Title siRNA for PDE4 sub-families 
Description at the very start of siRNA being developed we generated reagents to knock down specific sub-families. 
Type Of Material Technology assay or reagent 
Year Produced 2008 
Provided To Others? Yes  
Impact We used these novel reagents to great effect in altering people's perception of the functioning of PDE4 subfamilies by showing that they had non-redundant roles in cells. Extremely beneficial collaborations that have greatly aided our research. 
 
Description Anchored cAMP Signalling (1) 
Organisation University of Oslo
Country Norway 
Sector Academic/University 
PI Contribution Expertise in PDE4 biology.
Collaborator Contribution Reagent exchange. Knowledge of immunology.
Impact Reagent and expertise exchange. Joint publications. Partner in listed EU grants 15470025 15905070 16828089
 
Description Anchored cAMP Signalling (2) 
Organisation Leibniz Association
Department Leibniz-Institute for Molecular Pharmacology
Country Germany 
Sector Public 
PI Contribution Expertise in PDE4 biology.
Collaborator Contribution Reagent and expertise exchange. Joint publications. Partner in listed EU grants
Impact Reagent and expertise exchange. Joint publications. Partner in listed EU grants 16030021 16246107 16500722 16689683 17135396 17288540 17576803
 
Description Anchored cAMP Signalling (3) 
Organisation University of Kassel
Country Germany 
Sector Academic/University 
PI Contribution Expertise in PDE4 biology.
Collaborator Contribution Reagent and expertise exchange. Joint publications.
Impact Reagent and expertise exchange. Joint publications. Partner in listed EU grants 17088426
 
Description Anchored cAMP Signalling (4) 
Organisation University of Padova
Country Italy 
Sector Academic/University 
PI Contribution Expertise in PDE4 Biology. Immunological reagents
Collaborator Contribution Access to FRET technology for assessing cAMP levels in living cells
Impact Joint publications 15178638 15470025 16357307
 
Description Macrophages 
Organisation European Molecular Biology Laboratory
Department European Molecular Biology Laboratory Heidelberg
Country Germany 
Sector Public 
PI Contribution Expertise in PDE4 Biology and immunological reagents
Collaborator Contribution Access to a novel cell model
Impact Joint Publication 16931599
 
Description Memory and Learning (1) 
Organisation University of Pennsylvania
Country United States 
Sector Academic/University 
PI Contribution Expertise in PDE4 biology and reagents
Collaborator Contribution Access to in vivo models
Impact Publications 16738544 18230676 19847264
Start Year 2006
 
Description Memory and Learning (2) 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in PDE4 Biology. Reagents.
Collaborator Contribution Introduced us to a new scaffold system involving PDE4
Impact Joint Publications 16293762
 
Description Novel PDE4 isoforms 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution PDE4 biology expertise and enzymology expertise
Collaborator Contribution Bio-informatics analyses
Impact Joint publications 15025561 15738310
 
Description PDE4 Structure 
Organisation University of North Carolina at Chapel Hill
Country United States 
Sector Academic/University 
PI Contribution Expertsie in PDE4 Biology
Impact Joint Publication 17727341
Start Year 2006
 
Description PDE4 and colon cancer 
Organisation Beatson Institute for Cancer Research
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution PDE4 biology expertise and immunological reagents
Collaborator Contribution Novel cell lines for analysis
Impact Joint publication 15126637 17545604
 
Description PDE4 isoform function 
Organisation Novartis
Country Global 
Sector Private 
PI Contribution Expertise in PDE4 biology
Collaborator Contribution Antisera, siRNA reagents, selective PDE4 inhibitors, access to clinical samples
Impact Joint publications 12023945 12121997 15025561 15905070 16030021
 
Description PDE4 isoforms 
Organisation University of Alabama at Birmingham
Country United States 
Sector Academic/University 
PI Contribution Expertise in PDE4 biology and enzymology. Immunological reagents.
Collaborator Contribution Clones of a novel PDE4 isoform
Impact Joint publications 16689683 14500724 12810716 12441002 12435793 12193273
 
Description PDE4 structure (2) 
Organisation Heriot-Watt University
Country United Kingdom 
Sector Academic/University 
PI Contribution PDE4 biology
Collaborator Contribution Chemistry expertise
Impact Joint publication 12444918
 
Description PDE4D5 promoter 
Organisation Queen's Medical Centre
Country United Kingdom 
Sector Hospitals 
PI Contribution Expertise in PDE4 biology. PDE4 immunological reagents
Collaborator Contribution Access to a novel model system of clinical importance
Impact Joint publication 12121997
 
Description Press Release - DISC1 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact contributed to a press release concerning the role of mutant forms of the Disc1 scaffold protein to schizophrenia.

contacted by members of the public.
Year(s) Of Engagement Activity 2007
 
Description Press release - colon cancer 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact contributed to a press release indicating that PDE4 inhibitors and adenylyl cyclase activators could form a therapeutic approach for certain types of colon cancer.

contacted by members of the public and pharmaceutical industry.
Year(s) Of Engagement Activity 2007
 
Description School visit -Renfrewshire 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact talked to students about research in cell signalling and its biomedical importance.

hoped that this encouraged individuals on this career path. some individuals contacted me for advice.
Year(s) Of Engagement Activity 2006,2007,2008