Dipeptidyl peptidase IV: a cell surface peptidase involved in regulating T cell growth (review).
The CD26 antigen is identical with the cell surface ectopeptidase dipeptidyl peptidase IV (DP IV, EC 3.4.14.5). The post proline cleaving substrate specificity makes DP IV relatively unique among other proteases. Numerous cytokines, chemokines and other bioactive peptides are potential substrates of DP IV, but knowledge about the real in vivo substrates is still very limited. CD26 represents an accessory surface molecule playing an important role in the process of activation and proliferation of human lymphocytes. The molecular events mediated by this ectoenzyme are only partly established and the necessity of DP IV enzymatic activity for its signalling capacity has been controversial. This review out-lines evidence for an involvement of DP IV in the regulation of immune response and focuses on the putative role of the catalytic domain of this peptidase. Inhibition of the catalytic activity can provoke many cellular effects, including induction of tyrosine phosphorylations and p38 MAP kinase activation as well as suppression of DNA synthesis and reduced production of various cytokines. TGF-beta1, the production and secretion of which is increased after DP IV inhibition, supposedly mediates the observed suppressive effects by maintaining p27kip expression levels which leads to a cell cycle arrest in G1. Moreover, anti-CD3-induced signalling pathways can be strongly affected by DP IV inhibition. Thus, the enzymatic activity or at least the interaction of effectors with the catalytic domain of CD26 seem to be important for crucial functions of this cell surface antigen.
Kahne
T
T
Department of Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany.
Lendeckel
U
U
Wrenger
S
S
Neubert
K
K
Ansorge
S
S
Reinhold
D
D
D000243:Adenosine Deaminase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008954:Models, Biological; D015398:Signal Transduction; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
D016207:Cytokines; D004791:Enzyme Inhibitors; D008024:Ligands; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase