title: Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation.
abstract: Tyrosine kinases indirectly raise intracellular calcium concentration ([Ca2+]i) by activating phospholipases that generate inositol 1,4,5-trisphosphate (IP3). IP3 activates the IP3 receptor (IP3R), an intracellular calcium release channel on the endoplasmic reticulum. T cell receptor stimulation triggered a physical association between the nonreceptor protein tyrosine kinase Fyn and the IP3R, which induced tyrosine phosphorylation of the IP3R. Fyn activated an IP3-gated calcium channel in vitro, and tyrosine phosphorylation of the IP3R during T cell activation was reduced in thymocytes from fyn-/- mice. Thus, activation of the IP3R by tyrosine phosphorylation may play a role in regulating [Ca2+]i.
authors.affiliation: Laboratory for Molecular Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York 10029, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jayaraman
authors.forename: K
authors.initials: K
authors.lastname: Ondrias
authors.forename: E
authors.initials: E
authors.lastname: Ondriasová
authors.forename: A R
authors.initials: AR
authors.lastname: Marks
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism* / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D008213:Lymphocyte Activation; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000494:pharmacology; D051076:Proto-Oncogene Proteins c-fyn; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D019000:Phosphotyrosine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D002118:Calcium