Regulation and possible function of beta-catenin in human monocytes.
In this study, we demonstrate that adherence factors, serum constituents, LPS, and zymosan are capable of inducing a cellular accumulation of beta-catenin in human monocytes. Whereas adherence-dependent accumulation of beta-catenin can be blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, accumulation induced by the remaining stimuli cannot be prevented by inhibition of phosphatidylinositol 3-kinase, implying the involvement of beta-catenin in other not yet described signal transduction pathways. A role of beta-catenin in adherence-dependent processes by interacting with classical cadherins can be excluded as we could not detect cadherins in monocytes. To test whether it is possible that beta-catenin interacts with LEF/TCF (lymphoid enhancer factor/T cell factor) transcription factors, we studied the expression of this protein family. TCF-4 was identified as the LEF/TCF transcription factor present in human monocytes. However, neither cellular induction of beta-catenin nor cotransfection experiments with beta-catenin conducted in the monocytic cell line THP-1 resulted in the activation of a LEF/TCF-dependent promoter, suggesting the requirement of additional signals. Concurrent with this suggestion, we found that LPS and zymosan, two physiological inducers of beta-catenin, caused an increase in the expression of genes that are positively regulated by beta-catenin.
Thiele
A
A
Institute of Zoology, Department of Immunobiology, University of Leipzig, Leipzig, Germany.
Wasner
M
M
Müller
C
C
Engeland
K
K
Hauschildt
S
S
D000730:Androstadienes / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000077191:Wortmannin; D015054:Zymosan / Q000494:pharmacology; D051176:beta Catenin
D000730:Androstadienes; C495270:CTNNB1 protein, human; D015820:Cadherins; D003470:Culture Media; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D051821:Lymphoid Enhancer-Binding Factor 1; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; D015054:Zymosan; D000077191:Wortmannin