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 histocompat ibility complex class I (MHC-I) was explored in Jurkat T cells. Cross- linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Ja k1, Jak2, and Jak3. In addition, the transcription factor Stat-3 was t yrosine phosphorylated in the cytoplasma 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 interf eron-gamma activated site (GAS) in the c-fos promoter, a common DNA se quence 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-coupl ed agarose. io investigate the function of the activated Stat-3, Jurka t T cells were transiently transfected with a Stat-3 isoform lacking t he transactivating domain. This dominant-negative acting Stat-3 isofor m significantly inhibited apoptosis induced by ligation of MHC-I. In c onclusion, our data suggest the involvement of the Jak/Stat signal pat hway in MHC-I-induced signal transduction in T cells. (C) 1998 by The American Society of Hematology.