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 : 000060Inhibition 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 AnsorgeSource :
- Biochemical and Biophysical Research Communications [ 0006-291X ] ; 2000.
English descriptors
- KwdEn :
- Teeft :
- Academic press, Actinonin, Alanyl aminopeptidase, Aminopeptidase, Aminopeptidase inhibitors, Ansorge, Arndt, Biophysical research communications, Cell activation, Cell growth, Cell proliferation, Culture medium, England biolabs, Febs lett, Glycogen synthase, Idaho technology, Inhibitor, Lendeckel, Mrna, Mrna amounts, Mrna content, Pokeweed mitogen, Protein amounts, Quantitative determination, Strong increase, Trends genet, Upstate biotechnology.
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
Affiliations:
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<front><div type="abstract" xml:lang="en">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.</div>
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