A p56lck-independent pathway of CD2 signaling involves Jun kinase.
The p56 Src family non-receptor tyrosine kinase has been shown to be critical for T lymphocyte differentiation and activation. Hence in the absence of p56, T cell receptor triggered activation does not occur. We now provide evidence for a CD2-based signaling pathway which, in contrast to that of the T cell receptor, is independent of p56. CD2-mediated interleukin-2 production occurs via activation of Jun kinase in cell lines lacking p56. Jun kinase then facilitates the binding of c-Jun/c-Fos heterodimers to the AP-1 consensus site and the subsequent transcriptional activity of the interleukin-2 promoter. These data elucidate differences between TCR and CD2 signaling pathways in the same T cells.
Sunder-Plassmann
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Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Reinherz
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D015703:Antigens, CD / Q000502:physiology*; D018801:CD2 Antigens / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells / Q000166:cytology / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D018448:Models, Immunological; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D015703:Antigens, CD; D018801:CD2 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1; D019000:Phosphotyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases