title: The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling.
abstract: Antigen-specific activation of T lymphocytes, via stimulation of the T-cell antigen receptor (TCR) complex, is marked by a rapid and sustained increase in the concentration of cytoplasmic free Ca2+ ([Ca2+]i). It has been suggested that the second messenger inositol 1,4,5-trisphosphate (IP3) produced after TCR stimulation binds to the IP3 receptor (IP3R), an intracellular Ca(2+)-release channel, and triggers the increase in [Ca2+]i that activates transcription of the gene for T-cell growth factor interleukin 2 (IL-2). However, the role of the IP3R in T-cell signaling and possibly in plasma membrane Ca2+ influx in T cells remains unproven. Stable transfection of T cells (Jurkat) with antisense type 1 IP3R cDNA prevented type 1 IP3R expression, providing a tool for dissecting the role of IP3 signaling during T-cell activation. T cells lacking type 1 IP3R failed to increase [Ca2+]i or produce IL-2 after TCR stimulation. Moreover, depletion of intracellular Ca2+ stores without TCR activation stimulated Ca2+ influx in cells lacking the type 1 IP3R. These results establish that the type 1 IP3R is required for intracellular Ca2+ release that triggers antigen-specific T-cell proliferation but not for plasma membrane Ca2+ influx.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jayaraman
authors.forename: E
authors.initials: E
authors.lastname: Ondriasová
authors.forename: K
authors.initials: K
authors.lastname: Ondrias
authors.forename: D J
authors.initials: DJ
authors.lastname: Harnick
authors.forename: A R
authors.initials: AR
authors.lastname: Marks
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000096:biosynthesis / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D015290:Second Messenger Systems; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007376:Interleukin-2; D037181:Lectins, C-Type; D016376:Oligonucleotides, Antisense; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D000099192:CD69 Antigens; C506926:ITPR1 protein, human