actinonin and Lymphoma--T-Cell

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.

Topics: Calcium-Calmodulin-Dependent Protein Kinases; CD13 Antigens; Cell Line; Enzyme Induction; Gene Expression Regulation, Enzymologic; Humans; Hydroxamic Acids; Lymphoma, T-Cell; Mitogen-Activated Protein Kinase 1; Oligopeptides; Phosphorylation; Polymerase Chain Reaction; Protease Inhibitors; RNA, Messenger; T-Lymphocytes; Transcription, Genetic; Tumor Cells, Cultured