Activation of MAP-2 kinase activity by the CD2 receptor in Jurkat T cells can be reversed by CD45 phosphatase.
We have recently characterized a serine kinase in T lymphocytes which phosphorylates microtubule-associated protein-2 (MAP-2) in vitro. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves tyrosine phosphorylation of the enzyme itself. We show that the stimulatory anti-CD2 mAb combination, anti-(T11(2) + T11(3), stimulates MAP-2K activity in Jurkat cells with kinetics that are more prolonged than during anti-CD3 treatment. The principal difference is not in the rate of response induction, but in the decline of the response beyond the peak, to which end anti-CD2 stimulation resembles the sustained phytohaemagglutin (PHA) response. Parallel immunoblotting, utilizing anti-phosphotyrosine antibodies, also revealed differences in the rate at which tyrosine phosphorylation of pp43 (MAP-2K) disappears after induction. In spite of these differences, CD2 was absolutely dependent on the presence of CD3 for inducing a MAP-2K response in Jurkat cells. These results indicate that, even though CD2 and CD3 are using a common signalling pathway in Jurkat cells, additional differences such as the involvement of a tyrosine phosphatase may have to be considered in response generation. We also demonstrate that the common CD45 isoform, when cross-linked to CD2 by mAb, could inhibit the MAP-2K response during both induction as well as the disappearing phase of the response.
Department of Medicine, UCLA School of Medicine 90024-1680.
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Nel
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Ledbetter
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Williams
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Ho
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Akerley
K
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Franklin
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Katz
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015153:Blotting, Western; D018801:CD2 Antigens; D017252:CD3 Complex; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D015458:Leukemia, T-Cell / Q000276:immunology; D017493:Leukocyte Common Antigens; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000276:immunology; D011494:Protein Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D006649:Histocompatibility Antigens; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017493:Leukocyte Common Antigens