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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Organisations
- University of Glasgow, United Kingdom (Lead Research Organisation)
- European Molecular Biology Laboratory (Collaboration)
- University of Edinburgh, United Kingdom (Collaboration)
- University of Oslo, Norway (Collaboration)
- University of North Carolina at Chapel Hill (Collaboration)
- Queen's Medical Centre (Collaboration)
- University of Padova (Collaboration)
- AstraZeneca plc (Collaboration)
- University of Pennsylvania, United States (Collaboration)
- Novartis (Collaboration)
- Heriot-Watt University, United Kingdom (Collaboration)
- University of Alabama at Birmingham, United States (Collaboration)
- University of Kassel, Germany (Collaboration)
- Leibniz Association (Collaboration)
- Beatson Institute for Cancer Research, United Kingdom (Collaboration)
Publications
Abrahamsen H
(2004)
TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling.
in Journal of immunology (Baltimore, Md. : 1950)
Baillie GS
(2005)
Arrestin times for compartmentalised cAMP signalling and phosphodiesterase-4 enzymes.
in Current opinion in cell biology
Baillie GS
(2005)
Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract.
in FEBS letters
Barber R
(2004)
Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers.
in American journal of physiology. Lung cellular and molecular physiology
Bolger GB
(2006)
Scanning peptide array analyses identify overlapping binding sites for the signalling scaffold proteins, beta-arrestin and RACK1, in cAMP-specific phosphodiesterase PDE4D5.
in The Biochemical journal
Day JP
(2006)
A novel role for a Drosophila homologue of cGMP-specific phosphodiesterase in the active transport of cGMP.
in The Biochemical journal
Day JP
(2008)
Regulation of a Drosophila melanogaster cGMP-specific phosphodiesterase by prenylation and interaction with a prenyl-binding protein.
in The Biochemical journal
Day JP
(2005)
Cyclic nucleotide phosphodiesterases in Drosophila melanogaster.
in The Biochemical journal
Fleming YM
(2004)
PDE4-regulated cAMP degradation controls the assembly of integrin-dependent actin adhesion structures and REF52 cell migration.
in Journal of cell science
| Description | MRC Capacity Building Studentship |
| Amount | £58,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2007 |
| End | 09/2009 |
| Description | MRC Programme Grant |
| Amount | £1,900,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| 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 | Charity/Non Profit |
| 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 | Academic/University |
| 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 | Academic/University |
| 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 | Academic/University |
| 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 |