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
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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. / Skov, S; Nielsen, M; Bregenholt, S; Odum, Niels; Claesson, M H.
In: Blood, Vol. 91, No. 10, 1998, p. 3566-73.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Skov, S
AU - Nielsen, M
AU - Bregenholt, S
AU - Odum, Niels
AU - Claesson, M H
N1 - Keywords: Antibodies, Monoclonal; Apoptosis; Avidin; Biological Transport; Biotin; Cell Nucleus; Cytoplasm; DNA-Binding Proteins; Enzyme Activation; Gene Expression Regulation, Leukemic; Genes, fos; HLA Antigens; Humans; Interferon-gamma; Jurkat Cells; Lymphocyte Activation; Macromolecular Substances; Neoplasm Proteins; Phosphorylation; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proteins; Receptor-CD3 Complex, Antigen, T-Cell; Recombinant Fusion Proteins; STAT3 Transcription Factor; Signal Transduction; T-Lymphocytes; TYK2 Kinase; Trans-Activators; Transfection; beta 2-Microglobulin
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 9572990
VL - 91
SP - 3566
EP - 3573
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -
ID: 10635786