Signal transduction events induced or affected by inhibition of the catalytic activity of dipeptidyl peptidase IV (DP IV, CD26).
DP IV (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 discussed controversial. Focusing on the putative role of the catalytic domain of this peptidase, it could be shown that 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-beta 1, 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, including Ca2+ mobilisation, MEK1-, Erk1/2- and PKB-activation, 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 seems to be important for crucial functions of this cell surface antigen.
Kähne
T
T
Department of Internal Medicine, Otto-von-Guericke University Magdeburg, Germany.
Reinhold
D
D
Neubert
K
K
Born
I
I
Faust
J
J
Ansorge
S
S
D020013:Calcium Signaling / Q000187:drug effects*; D002384:Catalysis; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016853:Muromonab-CD3 / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D016853:Muromonab-CD3; D015842:Serine Proteinase Inhibitors; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D018819:Dipeptidyl Peptidase 4