Dipeptidyl peptidase IV: A cell surface peptidase involved in regulating Tcell growth (Review)

The CD26 antigen is identical with the cell surface ectopeptidase dipeptidy l peptidase IV (DP IV, EC 3.4.14.5). The post proline cleaving substrate sp ecificity makes DP IV relatively unique among other proteases. Numerous cyt okines, chemokines and other bioactive peptides are potential substrates of DP IV, but knowledge about the real ill vivo substrates is still very limi ted. CD26 represents an accessory surface molecule playing an important rol e in the process of activation and proliferation of human lymphocytes. The molecular events mediated by this ectoenzyme are only partly established an d the necessity of DP IV enzymatic activity for its signalling capacity has been controversial. This review outlines evidence for an involvement of DP IV in the regulation of immune response and focuses on the putative role o f the catalytic domain of this peptidase. Inhibition of the catalytic activ ity can provoke many cellular effects, including induction of tyrosine phos phorylations and p38 MAP kinase activation as well as suppression of DNA sy nthesis and reduced production of various cytokines. TGF-beta 1, the produc tion and secretion of which is increased after DP TV inhibition, supposedly mediates the observed suppressive effects by maintaining p27(kip) expressi on levels which leads to a cell cycle arrest in G(1). Moreover, anti-CD3-in duced signalling pathways can be strongly affected by DP IV inhibition. Thu s, the enzymatic activity or at least the interaction of effecters with the catalytic domain of CD26 seem to be important for crucial functions of thi s cell surface antigen.