WeightNameValue
1000 Titel
  • High-affinity AKAP7δ–protein kinase A interaction yields novel protein kinase A-anchoring disruptor peptides
1000 Autor/in
  1. Hundsrucker, Christian |
  2. Krause, Gerd |
  3. Beyermann, Michael |
  4. Prinz, Anke |
  5. Zimmermann, Bastian |
  6. Diekmann, Oliver |
  7. Lorenz, Dorothea |
  8. Stefan, Eduard |
  9. Nedvetsky, Pavel |
  10. Dathe, Margitta |
  11. Christian, Frank |
  12. Mcsorley, Theresa |
  13. Krause, Eberhard |
  14. Mcconnachie, George |
  15. Herberg, Friedrich W. |
  16. Scott, John D. |
  17. Rosenthal, Walter |
  18. Klussmann, Enno |
1000 Erscheinungsjahr 2006
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2006-06-01
1000 Erschienen in
1000 Quellenangabe
  • 396(2): 297-306
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1462715/ |
  • http://doi.org/10.1042/BJ20051970 |
1000 Ergänzendes Material
  • http://www.biochemj.org/content/396/2/297.supplemental |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • PKA (protein kinase A) is tethered to subcellular compartments by direct interaction of its regulatory subunits (RI or RII) with AKAPs (A kinase-anchoring proteins). AKAPs preferentially bind RII subunits via their RII-binding domains. RII-binding domains form structurally conserved amphipathic helices with unrelated sequences. Their binding affinities for RII subunits differ greatly within the AKAP family. Amongst the AKAPs that bind RIIα subunits with high affinity is AKAP7δ [AKAP18δ; Kd (equilibrium dissociation constant) value of 31 nM]. An N-terminally truncated AKAP7δ mutant binds RIIα subunits with higher affinity than the full-length protein presumably due to loss of an inhibitory region [Henn, Edemir, Stefan, Wiesner, Lorenz, Theilig, Schmidtt, Vossebein, Tamma, Beyermann et al. (2004) J. Biol. Chem. 279, 26654–26665]. In the present study, we demonstrate that peptides (25 amino acid residues) derived from the RII-binding domain of AKAP7δ bind RIIα subunits with higher affinity (Kd=0.4±0.3 nM) than either full-length or N-terminally truncated AKAP7δ, or peptides derived from other RII binding domains. The AKAP7δ-derived peptides and stearate-coupled membrane-permeable mutants effectively disrupt AKAP–RII subunit interactions in vitro and in cell-based assays. Thus they are valuable novel tools for studying anchored PKA signalling. Molecular modelling indicated that the high affinity binding of the amphipathic helix, which forms the RII-binding domain of AKAP7δ, with RII subunits involves both the hydrophobic and the hydrophilic faces of the helix. Alanine scanning (25 amino acid peptides, SPOT technology, combined with RII overlay assays) of the RII binding domain revealed that hydrophobic amino acid residues form the backbone of the interaction and that hydrogen bond- and salt-bridge-forming amino acid residues increase the affinity of the interaction.
1000 Sacherschließung
lokal A (PKA) anchor
lokal A kinase-anchoring protein 7 (AKAP7)
lokal RII-binding domain
lokal molecular modelling
lokal aquaporin-2 (AQP2)
lokal peptide disruptor
lokal protein kinase
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/SHVuZHNydWNrZXIsIENocmlzdGlhbg==|https://frl.publisso.de/adhoc/creator/S3JhdXNlLCBHZXJk|https://frl.publisso.de/adhoc/creator/QmV5ZXJtYW5uLCBNaWNoYWVs|https://frl.publisso.de/adhoc/creator/UHJpbnosIEFua2U=|https://frl.publisso.de/adhoc/creator/WmltbWVybWFubiwgQmFzdGlhbg==|https://frl.publisso.de/adhoc/creator/RGlla21hbm4sIE9saXZlcg==|https://frl.publisso.de/adhoc/creator/TG9yZW56LCBEb3JvdGhlYQ==|http://orcid.org/0000-0003-3650-4713|https://frl.publisso.de/adhoc/creator/TmVkdmV0c2t5LCBQYXZlbA==|https://frl.publisso.de/adhoc/creator/RGF0aGUsIE1hcmdpdHRh|http://orcid.org/0000-0001-8208-5930|https://frl.publisso.de/adhoc/creator/TWNzb3JsZXksIFRoZXJlc2E=|https://frl.publisso.de/adhoc/creator/S3JhdXNlLCBFYmVyaGFyZA==|https://frl.publisso.de/adhoc/creator/TWNjb25uYWNoaWUsIEdlb3JnZQ==|https://frl.publisso.de/adhoc/creator/SGVyYmVyZywgRnJpZWRyaWNoIFcu|https://frl.publisso.de/adhoc/creator/U2NvdHQsIEpvaG4gRC4=|https://frl.publisso.de/adhoc/creator/Um9zZW50aGFsLCBXYWx0ZXI=|https://frl.publisso.de/adhoc/creator/S2x1c3NtYW5uLCBFbm5v
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Bundesministerium für Forschung und Technik (BMBF) |
  3. European Union |
  4. - |
  5. National Institutes of Health |
1000 Fördernummer
  1. Ro597/9-1; Kl1415/1-1; Kl1415/2-1
  2. 01 GR 0441
  3. QLK3-CT-2002-02149
  4. -
  5. DK44239
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. Fonds der Chemischen Industrie
  5. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer Ro597/9-1; Kl1415/1-1; Kl1415/2-1
  2. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Forschung und Technik (BMBF) |
    1000 Förderprogramm -
    1000 Fördernummer 01 GR 0441
  3. 1000 joinedFunding-child
    1000 Förderer European Union |
    1000 Förderprogramm -
    1000 Fördernummer QLK3-CT-2002-02149
  4. 1000 joinedFunding-child
    1000 Förderer - |
    1000 Förderprogramm Fonds der Chemischen Industrie
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm -
    1000 Fördernummer DK44239
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6405102.rdf
1000 Erstellt am 2017-10-20T15:28:08.125+0200
1000 Erstellt von 25
1000 beschreibt frl:6405102
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Mar 08 13:44:18 CET 2018
1000 Objekt bearb. Thu Mar 08 13:44:18 CET 2018
1000 Vgl. frl:6405102
1000 Oai Id
  1. oai:frl.publisso.de:frl:6405102 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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