AKAP79/150 interacts with AC8 and regulates Ca2+-dependent cAMP synthesis in pancreatic and neuronal systems

Debbie Willoughby, Nanako Masada, Sebastian Wachten, Mario Pagano, Michelle Halls, Katy Everett, Antonio Ciruela, Dermot Cooper

Research output: Contribution to journalArticleResearchpeer-review

65 Citations (Scopus)

Abstract

Protein kinase A anchoring proteins (AKAPs) provide the backbone for targeted multimolecular signaling complexes that serve to localize the activities of cAMP. Evidence is accumulating of direct associations between AKAPs and specific adenylyl cyclase (AC) isoforms to facilitate the actions of protein kinaseA on cAMP production. It happens that some of the AC isoforms (AC1 and AC5/6) that bind specific AKAPs are regulated by submicromolar shifts in intracellular Ca2 . However, whether AKAPs play a role in the control of AC activity by Ca2 is unknown. Using a combination of co-immunoprecipitation and high resolution live cell imaging techniques, we reveal an association of the Ca2 -stimulable AC8 with AKAP79/150 that limits the sensitivity of AC8 to intracellular Ca2 events. This functional interaction between AKAP79/150 and AC8 was observed in HEK293 cells overexpressing the two signaling molecules. Similar findings were made in pancreatic insulin-secreting cells and cultured hippocampal neurons that endogenously express AKAP79/150 and AC8, which suggests important physiological implications for this protein-protein interaction with respect to Ca2 -stimulated cAMP production.
Original languageEnglish
Pages (from-to)20328 - 20342
Number of pages15
JournalJournal of Biological Chemistry
Volume285
Issue number26
DOIs
Publication statusPublished - 2010

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