title: Enzymatic activity of DPIV/CD26 is involved in PMA-induced hyperphosphorylation of p56lck.
abstract: The T-cell activation antigen CD26 (dipeptidyl peptidase IV, DPIV) is a proline specific protease thought to be involved in regulation of the immune response. Several former results characterized this ectoenzyme as a possible accessory molecule of the T-cell surface. The molecular events of lymphocyte activation mediated by this enzyme, as well as the physiological ligands of dipeptidyl peptidase, are only partly established. Here we provide evidence for a direct involvement of DPIV/CD26 in early phosphorylation mechanisms which were known to be essential in the signal transduction cascade of human T lymphocytes. Considering a possible functional linkage between CD26 and the tyrosine kinase p56lck, we have investigated the action of DPIV-specific inhibitors (Lys[Z[NO2)]-thiazolidide and -piperidide) on the PMA-induced hyperphosphorylation of p56lck in human T cells. Interestingly, this hyperphosphorylation of p56lck was strongly suppressed by both inhibitors in a dose-dependent manner. Removal of these inhibitors totally restored the hyperphosphorylation. Therefore, this effect could be considered as reversible. Free thiazolidine and piperidine, used in control experiments, neither inhibit DPIV enzyme activity nor PMA-induced hyperphosphorylation. The data presented here provide evidence that DPIV/CD26 is directly involved in early processes of T-cell activation. Furthermore, these findings strongly support the assumption that the signaling function of CD26 requires its enzymatic activity.
authors.affiliation: Institute of Experimental Internal Medicine, University of Magdeburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kähne
authors.forename: K
authors.initials: K
authors.lastname: Neubert
authors.forename: S
authors.initials: S
authors.lastname: Ansorge
mesh_terms: D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism*
chemical_list: D010880:Piperidines; D011480:Protease Inhibitors; D013844:Thiazoles; C093631:lysyl-(Z(nitro))piperidide; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D011493:Protein Kinase C; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D008239:Lysine; D013755:Tetradecanoylphorbol Acetate