Early Phosphorylation Events Induced by DPIV/CD26-Specific Inhibitors

• Published in: Cellular immunology 1998-10, Vol.189 (1), p.60-66
• Main Authors: Kähne, Thilo, Neubert, Klaus, Faust, Jürgen, Ansorge, Siegfried
• Format: Article
• Language: English
• Subjects: Calcium - metabolism; CD26; CD3 Complex - metabolism; Cyclic AMP - metabolism; Dipeptidyl Peptidase 4 - metabolism; dipeptidyl peptidase IV; Humans; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism; Lysine - analogs & derivatives; Lysine - pharmacology; Mitogens - pharmacology; Phosphorylation; Piperidines - pharmacology; Protease Inhibitors - pharmacology; Protein Kinase C - metabolism; protein tyrosine phosphorylation; T-Lymphocytes - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Thiazoles - pharmacology; Tyrosine - metabolism
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1998.1355

Dipeptidyl peptidase IV (DPIV, CD26) is known to be involved in the regulation of T lymphocyte and NK cell activation and proliferationin vitro.The molecular events of lymphocyte activation mediated by this ectopeptidase as well as their physiological ligands are only partly established. Particularly, the necessity of catalytic dipeptidase activity for the costimulatory function of this molecule has been controversial. Here we provide evidence for a direct involvement of DPIV/CD26 in early phosphorylation mechanisms which are known to be essential in the signal transduction cascade of human T lymphocytes. We have found that DPIV-specific inhibitors (Lys[Z(NO2)]-thiazolidide and -piperidide) are capable of inducing intracellular tyrosine phosphorylation in resting human T cells. On the other hand, both inhibitors decreased the PMA-induced tyrosine phosphorylation in human T cells in a dose-dependent manner. Furthermore, a linkage between CD26 and the tyrosine kinase p56lckwas shown by inhibition of PMA-induced hyperphosphorylation of p56lckby means of DPIV-specific inhibitors. The data presented here suggest that the inhibition of DPIV enzymatic activity induces a inhibitory signal transmitted by tyrosine kinases which leads to a block in a PMA-induced downstream pathway. These results support the assumption that DPIV/CD26 is directly involved in early processes of T cell activation via its enzymatic activity.