Galectin-induced activation of the transcription factors NFAT and AP-1 in human Jurkat T-lymphocytes.
Galectin-mediated ligation of glycoepitopes on T-cell activation markers induces an increase in the cytosolic calcium concentration ([Ca(2+)](i)) originating from a transient Ca(2+) release of internal stores as well as a sustained influx across the plasma membrane. In transiently transfected Jurkat T-lymphocytes, galectins [galectin-1 (gal-1), recombinant human galectin-1 (rec gal-1), nematode 32-kDa galectin (LEC-1), nematode 16-kDa galectin (LEC-6)] differentially stimulate the expression of the luciferase reporter gene constructs pNFAT-TA-Luc and pAP1(PMA)-TA-Luc, which are activated by the nuclear factor of activated T-cells (NFAT) or the transcription factor, activator protein 1 (AP-1), respectively. The galectin-stimulated expression of the reporter constructs is completely inhibited by lactose (30 mM) and asialofetuin (30 microM) carrying Galbeta1-4GlcNAc sequences. Preincubation of pNFAT-TA-Luc-transfected cells with cyclosporine A (0.1 microM) and FK506 (0.01 microM) abrogated the gal-1-induced expression of the reporter luciferase (Luc). Electrophoretic mobility shift assays (EMSAs) provided evidence for gal-1-stimulated increase in the binding of nuclear extracts to a synthetic oligonucleotide with an AP-1 consensus sequence.
Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Schillingallee 70, D-18057 Rostock, Germany. hermann.walzel@med.uni-rostock.de
Hermann
H
Walzel
Matthias
M
Blach
Jun
J
Hirabayashi
Yoichiro
Y
Arata
Ken-ichi
K
Kasai
Josef
J
Brock
D001212:Asialoglycoproteins / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D060748:Fetuins; D037483:Galectin 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D017930:Genes, Reporter / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007785:Lactose / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D000073718:Pancreatitis-Associated Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000494:pharmacology
D001212:Asialoglycoproteins; D004268:DNA-Binding Proteins; D060748:Fetuins; D037483:Galectin 1; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000509:alpha-Fetoproteins; C017029:asialofetuin; D016572:Cyclosporine; D007785:Lactose; D016559:Tacrolimus