Regulation by Ca2+-signaling pathways of adenylyl cyclases.
Interplay between the signaling pathways of the intracellular second messengers, cAMP and Ca(2+), has vital consequences for numerous essential physiological processes. Although cAMP can impact on Ca(2+)-homeostasis at many levels, Ca(2+) either directly, or indirectly (via calmodulin [CaM], CaM-binding proteins, protein kinase C [PKC] or Gβγ subunits) may also regulate cAMP synthesis. Here, we have evaluated the evidence for regulation of adenylyl cyclases (ACs) by Ca(2+)-signaling pathways, with an emphasis on verification of this regulation in a physiological context. The effects of compartmentalization and protein signaling complexes on the regulation of AC activity by Ca(2+)-signaling pathways are also addressed. Major gaps are apparent in the interactions that have been assumed, revealing a need to comprehensively clarify the effects of Ca(2+) signaling on individual ACs, so that the important ramifications of this critical interplay between Ca(2+) and cAMP are fully appreciated.
Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, United Kingdom.
Michelle L
ML
Halls
Dermot M F
DM
Cooper
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D008954:Models, Biological; D010802:Phylogeny; D020033:Protein Isoforms / Q000378:metabolism
D020033:Protein Isoforms; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium