Inhibition of alanyl-aminopeptidase suppresses the activation-dependent induction of glycogen synthase kinase-3beta (GSK-3beta) in human T cells
| Autor: | Uwe Lendeckel, Bernard P. Roques, K Frank, Beate Scholz, Siegfried Ansorge, Antje Spiess, Huixiong Chen, Marco Arndt |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
T cell
T-Lymphocytes Blotting Western Biophysics Biology CD13 Antigens Hydroxamic Acids Lymphocyte Activation Biochemistry Wnt-5a Protein chemistry.chemical_compound Glycogen Synthase Kinase 3 Phosphoserine GSK-3 Proto-Oncogene Proteins medicine Humans Protease Inhibitors RNA Messenger Amino Acids Phosphorylation Phytohemagglutinins Actinonin Glycogen synthase Molecular Biology Cells Cultured Cell growth Reverse Transcriptase Polymerase Chain Reaction Pokeweed mitogen Wnt signaling pathway Glycogen Synthase Kinases Imidazoles Cell Biology Molecular biology Wnt Proteins medicine.anatomical_structure chemistry Pokeweed Mitogens Enzyme Induction Calcium-Calmodulin-Dependent Protein Kinases biology.protein Growth inhibition Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 273(1) |
| ISSN: | 0006-291X |
| Popis: | 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-3beta (GSK-3beta). T cell activation by phytohaemagglutinin or pokeweed mitogen results in a strong increase of GSK-3beta mRNA amounts. At the protein level, we observed an up-regulation of both GSK-3beta and phosphorylated GSK-3beta. This induction-dependent increase of GSK-3beta 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. |
| Databáze: | OpenAIRE |
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