Differential roles of ERK and p38 MAP kinase pathways in positive and negative selection of T lymphocytes.
Clonal selection of T lymphocytes is essential for establishing self/non-self discrimination of immune recognition. It is known that cell surface signals such as avidity and valency of TCR-ligand interactions influence the fate of individual thymocytes, founding a primary repertoire of T cells. However, intracellular signals that govern positive and negative selection in the thymus have been unclear. The present study using the retroviral gene transfer technique shows that MKK1 activation in developing T cells is sufficient for providing positive selection signals. We also show that the MKK6-p38 signaling pathway is critically involved in inducing negative selection of thymocytes. These results suggest that intracellular signals through different MAP kinase cascades selectively guide positive and negative selection of T lymphocytes.
Sugawara
T
T
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.
Moriguchi
T
T
Nishida
E
E
Takahama
Y
Y
D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases
D017931:DNA Primers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one