PMID: 9639573Jun 26, 1998Paper

cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and changes in rolipram inhibition triggered by protein kinase A phosphorylation of Ser-54: generation of a molecular model

The Biochemical Journal
R HoffmannM D Houslay

Abstract

Ser-13 and Ser-54 were shown to provide the sole sites for the protein kinase A (PKA)-mediated phosphorylation of the human cAMP-specific phosphodiesterase isoform HSPDE4D3. The ability of PKA to phosphorylate and activate HSPDE4D3 was mimicked by replacing Ser-54 with either of the negatively charged amino acids, aspartate or glutamate, within the consensus motif of RRES54. The PDE4 selective inhibitor rolipram ¿4-[3-(cyclopentoxy)-4-methoxyphenyl]-2-pyrrolidone¿ inhibited both PKA-phosphorylated HSPDE4D3 and the Ser-54-->Asp mutant, with an IC50 value that was approximately 8-fold lower than that seen for the non-PKA-phosphorylated enzyme. Lower IC50 values for inhibition by rolipram were seen for a wide range of non-activated residue 54 mutants, except for those which had side-chains able to serve as hydrogen-bond donors, namely the Ser-54-->Thr, Ser-54-->Tyr and Ser-54-->Cys mutants. The Glu-53-->Ala mutant exhibited an activity comparable with that of the PKA phosphorylated native enzyme and the Ser-54-->Asp mutant but, in contrast to the native enzyme, was insensitive to activation by PKA, despite being more rapidly phosphorylated by this protein kinase. The activated Glu-53-->Ala mutant exhibited a sensitivity to inhibit...Continue Reading

Citations

Jan 24, 2004·Leukemia & Lymphoma·Arjen-Kars BoerEdo Vellenga
Feb 13, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Chunyan ChenFei Liao
Dec 17, 2009·Expert Opinion on Investigational Drugs·Rajkumar SavaiRalph Theo Schermuly
Jun 18, 2005·NeuroImage·Masahiro FujitaRobert B Innis
May 17, 2015·Endocrine-related Cancer·Rodrigo B de AlexandreFabio R Faucz
Jul 27, 1999·Current Opinion in Chemical Biology·A M Doherty
Nov 1, 2005·Drug Discovery Today·Miles D HouslayKam Y J Zhang
Apr 24, 2012·Cellular Signalling·Jurgen VandammeJohan M Thevelein
Nov 6, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Mark E GurneyAlex B Burgin
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Jennifer J Carlisle Michel, John D Scott
Mar 25, 2017·International Journal of Molecular Sciences·Eric P KnottDamien D Pearse
Aug 18, 2004·Neurochemistry International·Karnam S Murthy
Feb 20, 2002·FEBS Letters·France LalibertéZheng Huang
Apr 29, 2006·Circulation Research·Kimberly L Dodge-KafkaJohn D Scott
Feb 20, 2007·Circulation Research·Kenji Omori, Jun Kotera
Nov 23, 2005·Expert Opinion on Therapeutic Targets·Kam Y J ZhangGideon Bollag
Apr 30, 2011·Physiological Reviews·Sharron H FrancisJackie D Corbin
Dec 2, 2011·Clinical Pharmacology and Therapeutics·J M MichalskiS I Rennard
Feb 8, 2002·American Journal of Physiology. Cell Physiology·Karnam S MurthyGabriel M Makhlouf
Aug 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Roy S SongSusana R Neves
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.