Inhibition of alanyl aminopeptidase induces MAP-kinase p42/ERK2 in the human T cell line KARPAS-299.
Inhibition of alanyl aminopeptidase (EC 3.4.11.2, aminopeptidase N, CD13) expression, or activity compromise cell proliferation in a number of cell systems [1, 2, 3, 4, 5, 6]. The underlying mechanisms and the molecular components involved have not been identified as yet. In this study we show that inhibition of alanyl aminopeptidase enzymatic activity decreases the proliferation rate of the CD13-positive T cell line Karpas-299. By using the ATLAS cDNA expression array (Clontech) we identified the p42/ERK2 MAP kinase as one downstream target of probestin, a potent inhibitor of alanyl aminopeptidase. Probestin and another specific aminopeptidase inhibitor, actinonin, in addition to their capability of inducing erk-2 mRNA levels, significantly increase p42 phosphorylation state. This is the first report on signal transduction components possibly mediating the growth-modulatory effects of alanyl aminopeptidase inhibitors.
Lendeckel
U
U
Center of Internal Medicine, Institute of Immunology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, Magdeburg, D-39120, Germany. Lendeckel@medizin.uni-magdeburg.de
Kähne
T
T
Arndt
M
M
Frank
K
K
Ansorge
S
S
D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D016399:Lymphoma, T-Cell; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006877:Hydroxamic Acids; D009842:Oligopeptides; D011480:Protease Inhibitors; D012333:RNA, Messenger; C063432:probestin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D018826:CD13 Antigens; C010531:actinonin