Modulation of CD45 tyrosine phosphatase activity by antigen.
CD45 is a widely distributed phosphatase which modulates the activity of Lck by controlling the phosphorylation status of two tyrosine residues localized in the catalytic activation loop and in the negative regulatory domain. Little is known about the regulation of CD45 activity upon T cell activation. In the present study, we found that, in resting lymphocytes, an enzymatically active fraction of CD45 molecules is associated to the CD4 coreceptor. TCR engagement by an agonist ligand markedly inhibited this pool of CD45 phosphatase without affecting the CD4 / CD45 association. These results reveal that the modulation of the CD4-associated CD45 phosphatase activity is a very early biochemical event triggered by TCR stimulation. Since the recruitment of CD4 is an initial step in the activation process, the inhibition of this pool of CD45 molecules would be crucial to prevent dephosphorylation of relevant substrates which promote the activation process.
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy.
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Lago Paz
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Galgani
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D002999:Clone Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D000941:Antigens; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens