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J. Biol. Chem.-2011-Christian-9079-96.pdf 3,32MB
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1000 Titel
  • Small Molecule AKAP-Protein Kinase A (PKA) Interaction Disruptors That Activate PKA Interfere with Compartmentalized cAMP Signaling in Cardiac Myocytes
1000 Autor/in
  1. Christian, Frank |
  2. Szaszák, Márta |
  3. Friedl, Sabine |
  4. Drewianka, Stephan |
  5. Lorenz, Dorothea |
  6. Goncalves, Andrey |
  7. Furkert, Jens |
  8. Vargas, Carolyn |
  9. Schmieder, Peter |
  10. Götz, Frank |
  11. Zühlke, Kerstin |
  12. Moutty, Marie |
  13. Göttert, Hendrikje |
  14. Joshi, Mangesh |
  15. Reif, Bernd |
  16. Haase, Hannelore |
  17. Morano, Ingo |
  18. Grossmann, Solveig |
  19. Klukovits, Anna |
  20. Verli, Judit |
  21. Gáspár, Róbert |
  22. Noack, Claudia |
  23. Bergmann, Martin |
  24. Kass, Robert |
  25. Hampel, Kornelia |
  26. Kashin, Dmitry |
  27. Genieser, Hans-Gottfried |
  28. Herberg, Friedrich W. |
  29. Willoughby, Debbie |
  30. Cooper, Dermot M. F. |
  31. Baillie, George S. |
  32. Houslay, Miles D. |
  33. von Kries, Jens Peter |
  34. Zimmermann, Bastian |
  35. Rosenthal, Walter |
  36. Klussmann, Enno |
1000 Erscheinungsjahr 2010
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2010-12-22
1000 Erschienen in
1000 Quellenangabe
  • 286: 9079-9096
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2011
1000 Lizenz
1000 Verlagsversion
  • http://doi.org/10.1074/jbc.M110.160614 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058960/ |
1000 Ergänzendes Material
  • http://www.jbc.org/cgi/content/full/M110.160614/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • A-kinase anchoring proteins (AKAPs) tether protein kinase A (PKA) and other signaling proteins to defined intracellular sites, thereby establishing compartmentalized cAMP signaling. AKAP-PKA interactions play key roles in various cellular processes, including the regulation of cardiac myocyte contractility. We discovered small molecules, 3,3′-diamino-4,4′-dihydroxydiphenylmethane (FMP-API-1) and its derivatives, which inhibit AKAP-PKA interactions in vitro and in cultured cardiac myocytes. The molecules bind to an allosteric site of regulatory subunits of PKA identifying a hitherto unrecognized region that controls AKAP-PKA interactions. FMP-API-1 also activates PKA. The net effect of FMP-API-1 is a selective interference with compartmentalized cAMP signaling. In cardiac myocytes, FMP-API-1 reveals a novel mechanism involved in terminating β-adrenoreceptor-induced cAMP synthesis. In addition, FMP-API-1 leads to an increase in contractility of cultured rat cardiac myocytes and intact hearts. Thus, FMP-API-1 represents not only a novel means to study compartmentalized cAMP/PKA signaling but, due to its effects on cardiac myocytes and intact hearts, provides the basis for a new concept in the treatment of chronic heart failure.
1000 Sacherschließung
lokal AKAP150
lokal Signal Transduction
lokal Protein Kinase A (PKA)
lokal AKAP18
lokal Protein Phosphorylation
lokal Adenylate Cyclase (Adenylyl Cyclase)
lokal Yotiao
lokal Cyclic AMP (cAMP)
lokal Compartmentalized Signaling
lokal AKAP
lokal Protein-Protein Interactions
lokal Compartmentalization
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. http://orcid.org/0000-0001-8208-5930|https://frl.publisso.de/adhoc/creator/U3phc3rDoWssIE3DoXJ0YQ==|https://frl.publisso.de/adhoc/creator/RnJpZWRsLCBTYWJpbmU=|https://frl.publisso.de/adhoc/creator/RHJld2lhbmthLCBTdGVwaGFu|https://frl.publisso.de/adhoc/creator/TG9yZW56LCBEb3JvdGhlYQ==|https://frl.publisso.de/adhoc/creator/R29uY2FsdmVzLCBBbmRyZXk=|https://frl.publisso.de/adhoc/creator/RnVya2VydCwgSmVucw==|https://frl.publisso.de/adhoc/creator/VmFyZ2FzLCBDYXJvbHlu|http://orcid.org/0000-0001-9968-9327|https://frl.publisso.de/adhoc/creator/R8O2dHosIEZyYW5r|https://frl.publisso.de/adhoc/creator/WsO8aGxrZSwgS2Vyc3Rpbg==|https://frl.publisso.de/adhoc/creator/TW91dHR5LCBNYXJpZQ==|https://frl.publisso.de/adhoc/creator/R8O2dHRlcnQsIEhlbmRyaWtqZQ==|https://frl.publisso.de/adhoc/creator/Sm9zaGksIE1hbmdlc2g=|http://orcid.org/0000-0001-7368-7198|https://frl.publisso.de/adhoc/creator/SGFhc2UsIEhhbm5lbG9yZQ==|https://frl.publisso.de/adhoc/creator/TW9yYW5vLCBJbmdv|https://frl.publisso.de/adhoc/creator/R3Jvc3NtYW5uLCBTb2x2ZWln|https://frl.publisso.de/adhoc/creator/S2x1a292aXRzLCBBbm5h|https://frl.publisso.de/adhoc/creator/VmVybGksIEp1ZGl0|https://frl.publisso.de/adhoc/creator/R8Ohc3DDoXIsIFLDs2JlcnQ=|https://frl.publisso.de/adhoc/creator/Tm9hY2ssIENsYXVkaWE=|https://frl.publisso.de/adhoc/creator/QmVyZ21hbm4sIE1hcnRpbg==|https://frl.publisso.de/adhoc/creator/S2FzcywgUm9iZXJ0|https://frl.publisso.de/adhoc/creator/SGFtcGVsLCBLb3JuZWxpYQ==|https://frl.publisso.de/adhoc/creator/S2FzaGluLCBEbWl0cnk=|https://frl.publisso.de/adhoc/creator/R2VuaWVzZXIsIEhhbnMtR290dGZyaWVk|https://frl.publisso.de/adhoc/creator/SGVyYmVyZywgRnJpZWRyaWNoIFcu|https://frl.publisso.de/adhoc/creator/V2lsbG91Z2hieSwgRGViYmll|https://frl.publisso.de/adhoc/creator/Q29vcGVyLCBEZXJtb3QgTS4gRi4=|https://frl.publisso.de/adhoc/creator/QmFpbGxpZSwgR2VvcmdlIFMu|https://frl.publisso.de/adhoc/creator/SG91c2xheSwgTWlsZXMgRC4=|https://frl.publisso.de/adhoc/creator/dm9uIEtyaWVzLCBKZW5zIFBldGVy|https://frl.publisso.de/adhoc/creator/WmltbWVybWFubiwgQmFzdGlhbg==|https://frl.publisso.de/adhoc/creator/Um9zZW50aGFsLCBXYWx0ZXI=|https://frl.publisso.de/adhoc/creator/S2x1c3NtYW5uLCBFbm5vIA==
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. European Union |
  3. German Ministry of Education and Science |
  4. Medical Research Council UK |
  5. Fondation Leducq |
  6. Wellcome Trust |
1000 Fördernummer
  1. KL1415/4-1; KL1415/4-2
  2. 037189
  3. FKZ 0315097; 0315516
  4. G0600765
  5. 06CVD02
  6. RG31760
1000 Förderprogramm
  1. -
  2. -
  3. GoBio program
  4. -
  5. -
  6. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer KL1415/4-1; KL1415/4-2
  2. 1000 joinedFunding-child
    1000 Förderer European Union |
    1000 Förderprogramm -
    1000 Fördernummer 037189
  3. 1000 joinedFunding-child
    1000 Förderer German Ministry of Education and Science |
    1000 Förderprogramm GoBio program
    1000 Fördernummer FKZ 0315097; 0315516
  4. 1000 joinedFunding-child
    1000 Förderer Medical Research Council UK |
    1000 Förderprogramm -
    1000 Fördernummer G0600765
  5. 1000 joinedFunding-child
    1000 Förderer Fondation Leducq |
    1000 Förderprogramm -
    1000 Fördernummer 06CVD02
  6. 1000 joinedFunding-child
    1000 Förderer Wellcome Trust |
    1000 Förderprogramm -
    1000 Fördernummer RG31760
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6402709.rdf
1000 Erstellt am 2017-06-01T09:18:08.618+0200
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1000 Bearbeitet von 288
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1000 Objekt bearb. Wed Mar 31 07:06:49 CEST 2021
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