期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 273, 期 1, 页码 62-65出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/bbrc.2000.2883
关键词
alanyl aminopeptidase; CD13; cell proliferation; Wnt-5a; GSK-3 beta; quantitative PCR; lightcycler
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-3 beta (GSK-3 beta). T cell activation by phytohaemagglutinin or pokeweed mitogen results in a strong increase of GSK-3 beta mRNA amounts. At the protein level, we observed an upregulation of both GSK-3 beta and phosphorylated GSK-3 beta. This induction-dependent increase of GSK-3 beta 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. (C) 2000 Academic Press.
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