The PDZ protein erbin modulates beta-catenin-dependent transcription.
Erbin is a member of the leucine-rich repeat and PDZ domain family that can regulate proliferation, differentiation and cell adhesion. As a binding partner of the receptor tyrosine kinase ErbB2, erbin targets this receptor to the basolateral membrane of polarized epithelial cells. In addition, erbin is known to inhibit the Ras-mediated activation of the mitogen-activated protein kinase pathway. Recently we identified the proto-oncoprotein beta-catenin as a ligand of the PDZ domain of erbin. Here we demonstrate that erbin acts as a negative regulator of the beta-catenin/T-cell-factor-dependent gene expression. In contrast, a mutant of erbin with a deletion of the N-terminal leucine-rich repeat allows the PDZ domain of erbin to increase the beta-catenin/T-cell-factor-dependent transcription. This mutant localizes to the nucleus and mimics a putative splice variant found in keratinocytes. Thus, erbin has the potential to act as an inhibitor as well as an activator of the beta-catenin-regulated gene expression.
Ress
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Institute of Medical Virology, University of Zurich, Zurich, Switzerland. angelika.ress@gmx.net
Moelling
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D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D017930:Genes, Reporter; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D054731:PDZ Domains; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; C413364:ERBIN protein, human; D008024:Ligands; D011994:Recombinant Proteins; D051176:beta Catenin; D008156:Luciferases