MHC-I-induced apoptosis in human B-lymphoma cells is dependent on protein tyrosine and serine/threonine kinases.
In addition to providing the framework for peptide presentation, major histocompatibility complex class I (MHC-I) molecules can act as signal transducing molecules in lymphoid cells. Here we show that the mobilization of intracellular calcium, which follows crosslinking of MHC-I molecules on human B lymphoma cells, is dependent on protein tyrosine kinases and the phosphatidylinositol 3 (PI-3) kinase. Functional studies showed that MHC-I crosslinking induced almost complete inhibition of the spontaneous proliferation of the B lymphoma cells as early as 6 h post-crosslinking and apoptosis 24 h post-crosslinking. Preincubation with either protein tyrosine kinase or protein serine/threonine kinase inhibitors reduced the MHC-I-induced apoptosis to background levels, whereas inhibition of PI-3 kinase had no effect. These data demonstrate a pivotal role for protein tyrosine and serine/threonine kinases in MHC-I-mediated apoptosis in human B-cells and suggest the presence of several MHC-I signaling pathways leading to diverse effects in these cells.
Pedersen
A E
AE
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Building 18.3, Blegdamsvej 3, Copenhagen, DK-2200, Denmark.
Bregenholt
S
S
Johansen
B
B
Skov
S
S
Claesson
M H
MH
D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis; D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D047029:Lactams, Macrocyclic; D016393:Lymphoma, B-Cell / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D011940:Receptor Aggregation; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000077191:Wortmannin; D001613:beta 2-Microglobulin / Q000276:immunology
D000730:Androstadienes; D016227:Benzoquinones; D002118:Calcium; D002867:Chromones; D015395:Histocompatibility Antigens Class I; D047029:Lactams, Macrocyclic; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D011809:Quinones; D017828:Rifabutin; D000077191:Wortmannin; D001613:beta 2-Microglobulin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C020754:herbimycin