Blocked Ras activation in anergic CD4+ T cells.
T cell anergy is a state of functional unresponsiveness characterized by the inability to produce interleukin-2 (IL-2) upon T cell receptor stimulation. The mitogen-activated protein kinases ERK-1 and ERK-2 and the guanosine triphosphate-binding protein p21ras were found to remain unactivated upon stimulation of anergic murine T helper cell 1 clones. The inability to activate the Ras pathway did not result from a defect in association among Shc, Grb-2, and murine Son of Sevenless, nor from a defect in their tyrosine phosphorylation. This block in Ras activation may lead to defective transactivation at activator protein 1 sites in anergic cells and may enable T cells to shut down IL-2 production selectively during anergy.
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Ben May Institute, Department of Pathology, University of Chicago, IL 60637, USA.
Gajewski
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Fitch
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D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017635:Clonal Anergy; D002999:Clone Cells; D051380:GRB2 Adaptor Protein; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors
D048868:Adaptor Proteins, Signal Transducing; D015704:CD4 Antigens; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D007376:Interleukin-2; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D020663:ras Guanine Nucleotide Exchange Factors; D015759:Ionomycin; D006160:Guanosine Triphosphate; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras); D013755:Tetradecanoylphorbol Acetate