FMP Publications

Our publications are recorded in a searchable database since 2010, updates will be added regularly.

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References
Small molecule AKAP-protein kinase A (PKA) interaction disruptors that activate PKA interfere with compartmentalized cAMP signaling in cardiac myocytes
Christian, F., Szaszak, M., Friedl, S., Drewianka(*), S., Lorenz, D., Goncalves, A., Furkert, J., Vargas, C., Schmieder, P., Götz, F., Zühlke, K., Moutty, M., Göttert, H., Joshi, M., Reif, B., Haase(*), H., Morano(*), I., Grossmann, S., Klukovits(*), A., Verli(*), J., Gaspar(*), R., Noack(*), C., Bergmann(*), M., Kass(*), R., Hampel(*), K., Kashin(*), D., Genieser(*), H. G., Herberg(*), F. W., Willoughby(*), D., Cooper(*), D. M., Baillie(*), G. S., Houslay(*), M. D., von Kries, J. P., Zimmermann(*), B., Rosenthal(*), W.; Klussmann, E.
J Biol Chem, 286:9079-9096
(2011)

Tags: Anchored Signaling (Klussmann), Cellular Imaging (Wiesner), Solution NMR (Schmieder)

Abstract: 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 beta-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.

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Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
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