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• W2083977375 endingPage "7929" @default.
• W2083977375 startingPage "7917" @default.
• W2083977375 abstract "Calmodulin (CaM), by mediating the stimulation of the activity of two adenylyl cyclases (ACs), plays a key role in integrating the cAMP and Ca(2+) signaling systems. These ACs, AC1 and AC8, by decoding discrete Ca(2+) signals can contribute to fine-tuning intracellular cAMP dynamics, particularly in neurons where they predominate. CaM comprises an α-helical linker separating two globular regions at the N-terminus and the C-terminus that each bind two Ca(2+) ions. These two lobes have differing affinities for Ca(2+), and they can interact with target proteins independently. This study explores previous indications that the two lobes of CaM can regulate AC1 and AC8 differently and thereby yield different responses to cellular transitions in [Ca(2+)](i). We first compared by glutathione S-transferase pull-down assays and offline nanoelectrospray ionization mass spectrometry the interaction of CaM and Ca(2+)-binding deficient mutants of CaM with the internal CaM binding domain (CaMBD) of AC1 and the two terminal CaMBDs of AC8. We then examined the influence of these three CaMBDs on Ca(2+) binding by native and mutated CaM in stopped-flow experiments to quantify their interactions. The three CaMBDs show quite distinct interactions with the two lobes of CaM. These findings establish the critical kinetic differences between the mechanisms of Ca(2+)-CaM activation of AC1 and AC8, which may underpin their different physiological roles." @default.
• W2083977375 created "2016-06-24" @default.
• W2083977375 creator A5021042326 @default.
• W2083977375 creator A5022900338 @default.
• W2083977375 creator A5064524946 @default.
• W2083977375 creator A5084158849 @default.
• W2083977375 creator A5087794452 @default.
• W2083977375 date "2012-09-21" @default.
• W2083977375 modified "2023-09-26" @default.
• W2083977375 title "Distinct Mechanisms of Calmodulin Binding and Regulation of Adenylyl Cyclases 1 and 8" @default.
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• W2083977375 doi "https://doi.org/10.1021/bi300646y" @default.
• W2083977375 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3466776" @default.
• W2083977375 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22971080" @default.
• W2083977375 hasPublicationYear "2012" @default.
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