UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions

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dc.authorscopusid57194694827
dc.authorscopusid7202795779
dc.authorscopusid57197987128
dc.authorscopusid7004540505
dc.authorscopusid7101891257
dc.authorscopusid16188193800
dc.contributor.authorBeard, Matthew B.
dc.contributor.authorOlsen, Aileen E.
dc.contributor.authorJones, Randy E.
dc.contributor.authorErdogan, Suat
dc.contributor.authorHouslay, Miles D.
dc.contributor.authorBolger, Graeme B.
dc.date.accessioned2024-09-19T15:48:46Z
dc.date.available2024-09-19T15:48:46Z
dc.date.issued2000
dc.departmentHatay Mustafa Kemal Üniversitesien_US
dc.description.abstractThe cAMP-specific phosphodiesterases (PDE4) enzymes contain unique 'signature' regions of amino acid sequence, called upstream conserved regions 1 and 2 (UCR1 and UCR2). UCR1 and UCR2 are located between the extreme amino- terminal region and the catalytic region of the PDE4 enzymes. The UCR1 of the PDE4D3 isoform was used as a 'bait' in a two-hybrid screen, which identified a PDE4D cDNA clone containing UCR2 and the catalytic region but not UCR1. Two-hybrid and 'pull down' analysis of constructs incorporating various regions of the PDE4D3 cDNA demonstrated that the carboxyl-terminal region of UCR1 interacted specifically with the amino-terminal region of UCR2. The interaction was blocked by mutations of two positively charged amino acids (Arg-98 and Arg-101 to alanine) located within an otherwise largely hydrophobic region of UCR1. Mutation of three negatively charged amino acids in UCR2 (Glu-146, Glu-147, and Asp-149, all to alanine) also blocked the interaction. The phosphorylation of UCR1 by cAMP-dependent protein kinase (PKA) in vitro attenuated the ability of UCR1 to interact with UCR2. Mutation of the PKA substrate site in UCR1 (Ser-54) to aspartic acid, which mimics the activation of PDE4D3 by PKA, profoundly reduced the interaction between UCR1 and UCR2. Our data are consistent with a model in which UCR1 and UCR2 act as independent domains whose interaction is determined by electrostatic interactions and which may be disrupted by PKA phosphorylation. We suggest that the UCR1 and UCR2 domains may form a module that interacts with and regulates the PDE4 catalytic region.en_US
dc.description.sponsorshipNational Institute of General Medical Sciences, NIGMS, (R01GM058553)en_US
dc.identifier.doi10.1074/jbc.275.14.10349
dc.identifier.endpage10358en_US
dc.identifier.issn0021-9258
dc.identifier.issue14en_US
dc.identifier.pmid10744723en_US
dc.identifier.scopus2-s2.0-0034616226en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage10349en_US
dc.identifier.urihttps://doi.org/10.1074/jbc.275.14.10349
dc.identifier.urihttps://hdl.handle.net/20.500.12483/15299
dc.identifier.volume275en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject3',5'-Cyclic-Nucleotide Phosphodiesteraseen_US
dc.subjectAmino Acid Sequenceen_US
dc.subjectAmino Acid Substitutionen_US
dc.subjectBinding Sitesen_US
dc.subjectCatalytic Domainen_US
dc.subjectCloning, Molecularen_US
dc.subjectConserved Sequenceen_US
dc.subjectDNA, Complementaryen_US
dc.subjectElectrostaticsen_US
dc.subjectHela Cellsen_US
dc.subjectHumansen_US
dc.subjectKineticsen_US
dc.subjectModels, Molecularen_US
dc.subjectMolecular Sequence Dataen_US
dc.subjectMutagenesis, Site-Directeden_US
dc.subjectProtein Conformationen_US
dc.subjectRecombinant Proteinsen_US
dc.subjectSequence Alignmenten_US
dc.subjectSequence Homology, Amino Aciden_US
dc.subjectAnimaliaen_US
dc.subjectamino aciden_US
dc.subjectcyclic AMPen_US
dc.subjectphosphodiesteraseen_US
dc.subjectprotein kinaseen_US
dc.subjectamino acid sequenceen_US
dc.subjectanimal cellen_US
dc.subjectarticleen_US
dc.subjectcarboxy terminal sequenceen_US
dc.subjectcontrolled studyen_US
dc.subjectenzyme active siteen_US
dc.subjectgene disruptionen_US
dc.subjectgene locationen_US
dc.subjectgene mutationen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectnonhumanen_US
dc.subjectnucleotide sequenceen_US
dc.subjectpriority journalen_US
dc.subjectprotein domainen_US
dc.subjectprotein familyen_US
dc.subjectprotein isolationen_US
dc.subjectprotein phosphorylationen_US
dc.subjectprotein protein interactionen_US
dc.titleUCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactionsen_US
dc.typeArticleen_US

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