1000 Titel
  • A key phosphorylation site in AC8 mediates regulation of Ca2+-dependent cAMP dynamics by an AC8–AKAP79–PKA signalling complex
1000 Autor/in
  1. Willoughby, Debbie |
  2. Halls, Michelle L. |
  3. Everett, Katy L. |
  4. Ciruela, Antonio |
  5. Skroblin, Philipp |
  6. Klussmann, Enno |
  7. Cooper, Dermot M. F. |
1000 Erscheinungsjahr 2013
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2013-02-18
1000 Erschienen in
1000 Quellenangabe
  • 125: 5850-5859
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575714/ |
  • http://doi.org/10.1242/jcs.111427 |
1000 Ergänzendes Material
  • http://jcs.biologists.org/content/125/23/5850.supplemental |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Adenylyl cyclase (AC) isoforms can participate in multimolecular signalling complexes incorporating A-kinase anchoring proteins (AKAPs). We recently identified a direct interaction between Ca2+-sensitive AC8 and plasma membrane-targeted AKAP79/150 (in cultured pancreatic insulin-secreting cells and hippocampal neurons), which attenuated the stimulation of AC8 by Ca2+ entry (Willoughby et al., 2010). Here, we reveal that AKAP79 recruits cAMP-dependent protein kinase (PKA) to mediate the regulatory effects of AKAP79 on AC8 activity. Modulation by PKA is a novel means of AC8 regulation, which may modulate or apply negative feedback to the stimulation of AC8 by Ca2+ entry. We show that the actions of PKA are not mediated indirectly via PKA-dependent activation of protein phosphatase 2A (PP2A) B56δ subunits that associate with the N-terminus of AC8. By site-directed mutagenesis we identify Ser-112 as an essential residue for direct PKA phosphorylation of AC8 (Ser-112 lies within the N-terminus of AC8, close to the site of AKAP79 association). During a series of experimentally imposed Ca2+ oscillations, AKAP79-targeted PKA reduced the on-rate of cAMP production in wild-type but not non-phosphorylatable mutants of AC8, which suggests that the protein–protein interaction may provide a feedback mechanism to dampen the downstream consequences of AC8 activation evoked by bursts of Ca2+ activity. This fine-tuning of Ca2+-dependent cAMP dynamics by targeted PKA could be highly significant for cellular events that depend on the interplay of Ca2+ and cAMP, such as pulsatile hormone secretion and memory formation.
1000 Sacherschließung
lokal Adenylyl cyclase
lokal PKA
lokal AKAP
lokal calcium
lokal phosphorylation
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/V2lsbG91Z2hieSwgRGViYmll|https://frl.publisso.de/adhoc/creator/SGFsbHMsIE1pY2hlbGxlIEwu|https://frl.publisso.de/adhoc/creator/RXZlcmV0dCwgS2F0eSBMLg==|https://frl.publisso.de/adhoc/creator/Q2lydWVsYSwgQW50b25pbw==|https://frl.publisso.de/adhoc/creator/U2tyb2JsaW4sIFBoaWxpcHA=|https://frl.publisso.de/adhoc/creator/S2x1c3NtYW5uLCBFbm5v|https://frl.publisso.de/adhoc/creator/Q29vcGVyLCBEZXJtb3QgTS4gRi4=
1000 Label
1000 Förderer
  1. Wellcome Trust |
1000 Fördernummer
  1. RG31760
1000 Förderprogramm
  1. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Wellcome Trust |
    1000 Förderprogramm -
    1000 Fördernummer RG31760
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403125.rdf
1000 Erstellt am 2017-06-16T14:16:40.329+0200
1000 Erstellt von 25
1000 beschreibt frl:6403125
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet Thu Aug 18 07:58:59 CEST 2022
1000 Objekt bearb. Wed Mar 31 07:30:30 CEST 2021
1000 Vgl. frl:6403125
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403125 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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