title: cAMP and Ca²⁺ signaling in secretory epithelia: crosstalk and synergism.
abstract: The Ca(2+) and cAMP/PKA pathways are the primary signaling systems in secretory epithelia that control virtually all secretory gland functions. Interaction and crosstalk in Ca(2+) and cAMP signaling occur at multiple levels to control and tune the activity of each other. Physiologically, Ca(2+) and cAMP signaling operate at 5-10% of maximal strength, but synergize to generate the maximal response. Although synergistic action of the Ca(2+) and cAMP signaling is the common mode of signaling and has been known for many years, we know very little of the molecular mechanism and mediators of the synergism. In this review, we discuss crosstalk between the Ca(2+) and cAMP signaling and the function of IRBIT (IP3 receptors binding protein release with IP3) as a third messenger that mediates the synergistic action of the Ca(2+) and cAMP signaling.
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, United States. Electronic address: Malini.ahuja@nih.gov.
authors.forename: Malini
authors.initials: M
authors.lastname: Ahuja
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, United States.
authors.forename: Archana
authors.initials: A
authors.lastname: Jha
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, United States.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Maléth
authors.affiliation: Department of Physiology, School of Medicine, Ewha Womans University, 911-1 Mok-6-dong, Yang Chun-gu, Seoul 158-710, Republic of Korea.
authors.forename: Seonghee
authors.initials: S
authors.lastname: Park
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, United States. Electronic address: Shmuel.muallem@nih.gov.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
mesh_terms: D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D026901:Membrane Transport Proteins; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Calcium signaling; Duct epithelia; IRBIT; Synergism