Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk
| Autor: | Richard L. Edelson, Maria Concetta Fargnoli, Clément Couture, Ruth Halaban, Tomas Mustelin, S. Chimenti, C. L. Berger |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Cancer Research Skin Neoplasms T-Lymphocytes Receptors Antigen T-Cell Syk Biology Immunophenotyping CSK Tyrosine-Protein Kinase chemistry.chemical_compound Cell surface receptor medicine Humans Syk Kinase Phosphotyrosine Enzyme Precursors ZAP-70 Protein-Tyrosine Kinase ZAP70 T-cell receptor Cutaneous T-cell lymphoma Intracellular Signaling Peptides and Proteins Tyrosine phosphorylation Hematology Protein-Tyrosine Kinases medicine.disease Lymphoma T-Cell Cutaneous Enzyme Activation src-Family Kinases Oncology chemistry Cancer research Phosphorylation Signal transduction Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0887-6924 |
| Popis: | Malignant cells of patients with cutaneous T cell lymphoma (CTCL) are of monoclonal origin and of the CD4 + /CD45RO + subset. Since unlike their normal counterparts, triggering of their TCRICD3 in vitro elicits only a weak mitogenic response, we set out to determine which of the signal transduction molecules initiated by anti-CD3e antibodies are affected in neoplastic cells. The results obtained from analysis of tumor cells from four patients show a general reduction in basal and induced tyrosine phosphorylation of a wide range of signaling proteins. Furthermore, the function of members from distinct families of protein tyrosine kinases was altered in neoplastic cells. The enzymatic activity of the membrane-bound fraction of Csk was suppressed, and its association with other cellular proteins was altered. There was a decline in the amount and activity of Syk, and a slight decrease in the specific activity of Lck kinases. Zap70 tyrosyl phosphorylation was reduced or undetectable and the kinase associated weakly, or not at all, with the TCR ζ chain. We propose that dampened TCR-triggered responses in CTCL are caused by suppression of an array of effector molecules required for coupling cell surface receptors to early and late signaling events. |
| Databáze: | OpenAIRE |
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