Signal transduction by HLA-DR is mediated by tyrosine kinase(s) and regulated by CD45 in activated T cells
| Autor: | Paul J. Martin, Niels Ødum, Jeffrey A. Ledbetter, Gary L. Schieven, Nancy A. Norris, Laura Sue Grosmaire, John A. Hansen |
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| Rok vydání: | 1991 |
| Předmět: |
Lactams
Macrocyclic T-Lymphocytes Immunology Protein tyrosine phosphatase Biology chemistry.chemical_compound Antigens CD Histocompatibility Antigens Benzoquinones Humans Immunology and Allergy Cells Cultured Protein kinase C T-cell receptor Quinones Tyrosine phosphorylation HLA-DR Antigens General Medicine Protein-Tyrosine Kinases Clone Cells Cell biology Enzyme Activation Rifabutin chemistry Biochemistry Herbimycin CD4 Antigens Leukocyte Common Antigens Phosphorylation Calcium Signal transduction Tyrosine kinase Signal Transduction |
| Zdroj: | Human Immunology. 32:85-94 |
| ISSN: | 0198-8859 |
| Popis: | Recently, it was shown that HLA class II molecules on B cells and activated human T cells can transmit signals involving tyrosine phosphorylation of specific proteins, activation of the inositol phospholipid pathway, and release of cytosolic free Ca2+(Ca2+)i. The regulation of class II induced signals is poorly understood, however, and it remained unknown whether these pathways were coupled or activated independently. Here we show that a specific inhibitor of protein tyrosine kinases (PTK), herbimycin, abrogated DR-induced elevation of (Ca2+)i in activated human T cells. Genistein, belonging to another family of PTK inhibitors, had weaker but significant inhibitory effects on DR-induced (Ca2+)i responses. CD45 crosslinking with DR almost completely abrogated DR-induced (Ca2+)i responses and profoundly changed the PTK profiles. In contrast, CD4 crosslinking with DR enhanced the (Ca2+)i responses, but the inhibitory effect of CD45 dominated over the enhancing effect of CD4. These data indicate that PTK activation is obligatory for DR-induced (Ca2+)i responses, suggesting a linkage between these pathways in class II signal transduction. This conclusion is consistent with our observation that in activated human T cells, class II signals are up regulated by CD4, which is associated with p56lck, and down regulated by CD45, which is a tyrosine phosphatase. |
| Databáze: | OpenAIRE |
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