Activation of Stat-3 is involved in the induction of apoptosis after ligation of major histocompatibility complex class I molecules on human Jurkat T cells.
Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasm and subsequently translocated to the cell nucleus. Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element (hSIE) DNA-probe derived from the interferon-gamma activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest the involvement of the Jak/Stat signal pathway in MHC-I-induced signal transduction in T cells.
Skov
S
S
Laboratory of Experimental Immunology, Department of Medical Anatomy, the Panum Institute, University of Copenhagen, Copenhagen, Denmark. s.skov@sb.immi.ku.dk
Nielsen
M
M
Bregenholt
S
S
Odum
N
N
Claesson
M H
MH
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001360:Avidin / Q000276:immunology; D001692:Biological Transport; D001710:Biotin / Q000276:immunology; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004789:Enzyme Activation; D015973:Gene Expression Regulation, Leukemic; D016762:Genes, fos; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D019169:Jurkat Cells / Q000201:enzymology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection; D001613:beta 2-Microglobulin / Q000276:immunology
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D006680:HLA Antigens; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D001613:beta 2-Microglobulin; D001360:Avidin; D001710:Biotin; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human