WeightNameValue
1000 Titel
  • Mapping binding sites for the PDE4D5 cAMP-specific phosphodiesterase to the N- and C-domains of β-arrestin using spot-immobilized peptide arrays
1000 Autor/in
  1. Baillie, George S. |
  2. Adams, David R. |
  3. Bhari, Narinder |
  4. Houslay, Thomas M. |
  5. Vadrevu, Suryakiran |
  6. Meng, Dong |
  7. Li, Xiang |
  8. Dunlop, Allan |
  9. Milligan, Graeme |
  10. Bolger, Graeme B. |
  11. Klussmann, Enno |
  12. Houslay, Miles D. |
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2007-05-15
1000 Erschienen in
1000 Quellenangabe
  • 404(1): 71-80
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868836/ |
  • http://doi.org/10.1042/BJ20070005 |
1000 Ergänzendes Material
  • http://www.biochemj.org/content/404/1/71.figures-only |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • β2-ARs (β2-adrenoceptors) become desensitized rapidly upon recruitment of cytosolic β-arrestin. PDE4D5 (family 4 cAMP-specific phosphodiesterase, subfamily D, isoform 5) can be recruited in complex with β-arrestin, whereupon it regulates PKA (cAMP-dependent protein kinase) phosphorylation of the β2-AR. In the present study, we have used novel technology, employing a library of overlapping peptides (25-mers) immobilized on cellulose membranes that scan the entire sequence of β-arrestin 2, to define the interaction sites on β-arrestin 2 for binding of PDE4D5 and the cognate long isoform, PDE4D3. We have identified a binding site in the β-arrestin 2 N-domain for the common PDE4D catalytic unit and two regions in the β-arrestin 2 C-domain that confer specificity for PDE4D5 binding. Alanine-scanning peptide array analysis of the N-domain binding region identified severely reduced interaction with PDE4D5 upon R26A substitution, and reduced interaction upon either K18A or T20A substitution. Similar analysis of the β-arrestin 2 C-domain identified Arg286 and Asp291, together with the Leu215–His220 region, as being important for binding PDE4D5, but not PDE4D3. Transfection with wild-type β-arrestin 2 profoundly decreased isoprenaline-stimulated PKA phosphorylation of the β2-AR in MEFs (mouse embryo fibroblasts) lacking both β-arrestin 1 and β-arrestin 2. This effect was negated using either the R26A or the R286A mutant form of β-arrestin 2 or a mutant with substitution of an alanine cassette for Leu215–His220, which showed little or no PDE4D5 binding, but was still recruited to the β2-AR upon isoprenaline challenge. These data show that the interaction of PDE4D5 with both the N- and C-domains of β-arrestin 2 are essential for β2-AR regulation.
1000 Sacherschließung
lokal β-arrestin
lokal desensitization
lokal β2-adrenoceptor
lokal phosphodiesterase 4 (PDE4)
lokal peptide array
lokal cAMP
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/QmFpbGxpZSwgR2VvcmdlIFMu|https://frl.publisso.de/adhoc/creator/QWRhbXMsIERhdmlkIFIu|https://frl.publisso.de/adhoc/creator/QmhhcmksIE5hcmluZGVy|https://frl.publisso.de/adhoc/creator/SG91c2xheSwgVGhvbWFzIE0u|https://frl.publisso.de/adhoc/creator/VmFkcmV2dSwgU3VyeWFraXJhbg==|https://frl.publisso.de/adhoc/creator/TWVuZywgRG9uZw==|https://frl.publisso.de/adhoc/creator/TGksIFhpYW5n|https://frl.publisso.de/adhoc/creator/RHVubG9wLCBBbGxhbg==|https://frl.publisso.de/adhoc/creator/TWlsbGlnYW4sIEdyYWVtZQ==|https://frl.publisso.de/adhoc/creator/Qm9sZ2VyLCBHcmFlbWUgQi4=|https://frl.publisso.de/adhoc/creator/S2x1c3NtYW5uLCBFbm5v|https://frl.publisso.de/adhoc/creator/SG91c2xheSwgTWlsZXMgRC4=
1000 Label
1000 Förderer
  1. Medical Research Council (U.K.) |
  2. Leducq Foundation |
  3. National Institutes of Health |
  4. Deutsche Forschungsgemeinschaft |
  5. European Union |
1000 Fördernummer
  1. G8604010; G0400053
  2. -
  3. R01-GM58553
  4. Kl1415/2
  5. 037189
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. -
  5. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Medical Research Council (U.K.) |
    1000 Förderprogramm -
    1000 Fördernummer G8604010; G0400053
  2. 1000 joinedFunding-child
    1000 Förderer Leducq Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm -
    1000 Fördernummer R01-GM58553
  4. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer Kl1415/2
  5. 1000 joinedFunding-child
    1000 Förderer European Union |
    1000 Förderprogramm -
    1000 Fördernummer 037189
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6404520.rdf
1000 Erstellt am 2017-09-20T15:30:34.508+0200
1000 Erstellt von 25
1000 beschreibt frl:6404520
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Fri Oct 21 18:50:03 CEST 2022
1000 Objekt bearb. Fri Oct 21 18:50:03 CEST 2022
1000 Vgl. frl:6404520
1000 Oai Id
  1. oai:frl.publisso.de:frl:6404520 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source