Expression of p56lck in B-cell neoplasias.
The protooncogene p56lck is considered to participate in malignant transformation of lymphoid cells. In order to evaluate the role of this tyrosine kinase in B cell neoplasias, we investigated the expression of p56lck by Western blot analysis. In 12/16 Burkitt's lymphoma derived cell lines, 3/3 lymphoblastoid cell lines, 1/6 Hodgkin's disease derived cell lines, and 10/10 freshly isolated chronic lymphocytic leukemia cells constitutive expression of the protein was detected. Protein tyrosine kinase assays detected a catalytic active form of p56lck in all p56lck expressing samples. Stimulation experiments of the different cell lines and primary tumour cells by the phorbol ester TPA and the B-cell specific stimulation with SAC/anti-IgM respectively indicated a change of the expression level in comparison with the unstimulated cells and, a higher molecular weight species of the protein tyrosine kinase p56lck was observed. This was probably due to hyperphosphorylation of p56lck. No correlation between an infection with the Epstein-Barr virus and the expression of p56lck was found in the cell lines used and in primary tumour cells. Inhibition of p56lck activity by the specific inhibitor 4-amino-6-hydroxyflavone revealed a decrease of proliferation of the T-cell line Jurkat, but not of the Burkitt's lymphoma cell lines. In the analysed cell lines we found a reduction of the kinase activity of p56lck of approximately 70%. These results suggest that lck may contribute to the maintenance of the transformation of the analysed B cell neoplasias but that lck does not support a model for an initial event in B cell transformation.
Von Knethen
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A
Klinik IV für Nephrologie, Universität Erlangen, Germany. mfm422@rzmail.uni-erlangen.de
Abts
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H
Kube
D
D
Diehl
V
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Tesch
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H
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000031:analogs & derivatives; D006367:HeLa Cells; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D013211:Staphylococcus aureus; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D004791:Enzyme Inhibitors; D005419:Flavonoids; C044203:anti-IgM; C067397:4'-amino-6-hydroxyflavone; D019833:Genistein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate