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Inhibition of Alanyl-Aminopeptidase Suppresses the Activation-Dependent Induction of Glycogen Synthase Kinase-3β (GSK-3β) in Human T Cells

Identifieur interne : 000059 ( France/Analysis ); précédent : 000058; suivant : 000060

Inhibition of Alanyl-Aminopeptidase Suppresses the Activation-Dependent Induction of Glycogen Synthase Kinase-3β (GSK-3β) in Human T Cells

Auteurs : Uwe Lendeckel ; Beate Scholz [Allemagne] ; Marco Arndt [Allemagne] ; Karin Frank ; Antje Spiess [Allemagne] ; Huixiong Chen [France] ; Bernard P. Roques [France] ; Siegfried Ansorge

Source :

RBID : ISTEX:72C5A439E086ADA4F61577B3086BB5C8812B0645

English descriptors

Abstract

Abstract: Inhibition of alanyl-aminopeptidase (APN, CD13) gene expression or enzymatic activity compromises T cell proliferation and function. Molecular mechanisms mediating these effects are not known as yet. Recently, we found the expression of the proto-oncogen Wnt-5a to be strongly affected by APN-inhibition. Wnt-5a and other members of the Wnt family of secreted factors are implicated in cell growth and differentiation. Here, we analyzed by quantitative RT-PCR and immunoblotting the expression in mitogen-activated T cells of a major constituent of the Wnt-5a pathway, glycogen synthase kinase-3β (GSK-3β). T cell activation by phytohaemagglutinin or pokeweed mitogen results in a strong increase of GSK-3β mRNA amounts. At the protein level, we observed an up-regulation of both GSK-3β and phosphorylated GSK-3β. This induction-dependent increase of GSK-3β is markedly reduced in response to inhibitors of alanyl-aminopeptidase, actinonin, leuhistin, and RB3014. These findings may provide a rational for the growth inhibition resulting from a diminished expression or activity of alanyl aminopeptidase.

Url:
DOI: 10.1006/bbrc.2000.2883


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ISTEX:72C5A439E086ADA4F61577B3086BB5C8812B0645

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