title: Regulation of Ca2+ release by cAMP-dependent protein kinase. A mechanism for agonist-specific calcium signaling?
abstract: Calcium is an ubiquitous second messenger that is involved in the regulation of a number of cell functions. The mechanism by which the specificity of calcium signaling is achieved is not well understood. We suggest that calcium release from the ER can occur selectively at different spatial locations in response to different extracellular stimuli. We discuss a possible mechanism for such selectivity and present a model based on this mechanism. The suggested mechanism is based on the regulation of local Ca2+ release by cyclic AMP-dependent protein kinase (PKA) and relies upon two experimental observations: first, some G-protein coupled signaling pathways activate PLC and regulate adenylate cyclase at the same time, leading to IP3 production and altering PKA activity via changes in cAMP level; second, phosphorylation by PKA alters the properties of IP3 receptor (IP3R). In our model we consider allosteric regulation of IP3Rs by IP3 and cAMP-dependent phosphorylation. The differences in IP3Rs and PKA densities at different spatial locations within the cell allow the release of calcium selectively at each location in response to certain combination of IP3 and cAMP concentration. Specificity of agonist-response coupling is achieved if different combinations in the levels of these second messengers are specific for different extracellular stimuli.
authors.affiliation: Institute of Theoretical Dynamics, University of California, Davis 95616, USA. andrej@itd.ucdavis.edu
authors.forename: A E
authors.initials: AE
authors.lastname: Bugrim
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium