MHC class I signaling in T cells leads to tyrosine kinase activity and PLC-gamma 1 phosphorylation.
We have studied the biochemical signal pathway leading to a rise in intracellular free calcium concentration ([Ca2+]i) following cross-linking of MHC class I (MHC-I) molecules on human T leukemic Jurkat cells. Evidence is presented that MHC-I signaling is dependent on tyrosine kinase activity before the observed increase in [Ca2+]i. Thus, tyrosine phosphorylation was detected within 5 s after MHC-I cross-linking, whereas an increase in [Ca2+]i was observed after a lag period of 30 s. Moreover, an inhibitor of tyrosine kinases, herbimycin A, almost completely blocked MHC-I-induced tyrosine phosphorylation and the subsequent calcium response. The early tyrosine kinase activity was found to be dependent on expression of the TCR/CD3 complex and the CD45 molecule on the surface of the T cells. Furthermore, MHC-I cross-linking was shown to tyrosine phosphorylate PLC-gamma 1 (phospholipase C-gamma 1). Collectively, these results indicate that the MHC-I signaling pathway is linked to activation of tyrosine kinase(s) in Jurkat cells.
Skov
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Department of Medical Anatomy, Panum Institute, University of Copenhagen, Denmark.
Odum
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Claesson
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D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D047029:Lactams, Macrocyclic; D017493:Leukocyte Common Antigens / Q000276:immunology; D051966:Phospholipase C gamma; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D016227:Benzoquinones; D015395:Histocompatibility Antigens Class I; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D011809:Quinones; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D017828:Rifabutin; D019000:Phosphotyrosine; D014443:Tyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium