Modulation of WNT-5A expression by actinonin: linkage of APN to the WNT-pathway?
Inhibition of alanyl-aminopeptidase gene expression or enzymatic activity compromises T cell proliferation and function. Molecular mechanisms mediating these effects are not known as yet. Applying the cDNA array technique we identified the proto-oncogen Wnt-5a strongly affected by APN-inhibition. Wnt-5a and other members of the Wnt family of secreted factors are implicated in cell growth and differentiation. Wnt-5a was moderately expressed in resting T cells, but strongly down-regulated in response to activation by OKT3/IL-4/IL-9. Actinonin increased Wnt-5a-mRNA contents as confirmed by RT-PCR. In addition, expression of GSK-3 beta, an inherent component of the Wnt-pathway, was found to be increased in response to activation, but suppressed by actinonin at both the mRNA and protein level. These findings may provide a rationale for the strong growth inhibitory effects resulting from an inhibition of alanyl aminopeptidase expression or activity.
Lendeckel
U
U
Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Germany.
Arndt
M
M
Frank
K
K
Spiess
A
A
Reinhold
D
D
Ansorge
S
S
D018826:CD13 Antigens / Q000096:biosynthesis* / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D016853:Muromonab-CD3 / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011480:Protease Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
D006877:Hydroxamic Acids; D016906:Interleukin-9; D007527:Isoenzymes; D016853:Muromonab-CD3; D011480:Protease Inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D015847:Interleukin-4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018826:CD13 Antigens; C010531:actinonin