Aminopeptidase N/CD13 is directly linked to signal transduction pathways in monocytes.
In the present study, we characterized in monocytes the rise in [Ca(2+)](i) evoked by monoclonal antibodies (mAbs) to aminopeptidase N (APN)/CD13, showing a two-phase calcium increase with a small-belled [Ca(2+)](i) rise due to the release of calcium from intracellular stores and a more sustained plateau due to the influx of calcium from the extracellular environment. Tyrosine kinase inhibitors were able to inhibit the rise in [Ca(2+)](i) induced by ligation APN/CD13, as were inhibitors of the phosphatidylinositol 3-kinase. For the first time we can show that mAbs to APN/CD13 provoke phosphorylation of the mitogen-activated protein kinases ERK1/2, JNK, and p38. Furthermore, we show that mRNA of the chemotactic cytokine IL-8 is upregulated under the influence of APN/CD13 ligation. Although the in vivo ligand as well as possible cooperating membrane molecules remains to be identified, our results suggest that the membrane ectoenzyme APN/CD13 is a novel signal transduction molecule in monocytes.
Santos
A N
AN
Institute of Medical Immunology, Martin Luther University, Strasse der OdF 6, Halle, D-06097, Germany.
Langner
J
J
Herrmann
M
M
Riemann
D
D
D000730:Androstadienes / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D018826:CD13 Antigens / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020298:U937 Cells; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D002867:Chromones; D016209:Interleukin-8; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins; D012333:RNA, Messenger; C073882:phosphoprotein phosphatase inhibitor 1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D018826:CD13 Antigens; D002118:Calcium; D000077191:Wortmannin