The PDZ Protein Erbin Modulates β-Catenin-Dependent Transcription

• Published in: European surgical research Vol. 41; no. 3; pp. 284 - 289
• Main Authors: Ress, A., Moelling, K.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.01.2008
• Subjects: Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; beta Catenin - chemistry; beta Catenin - genetics; beta Catenin - metabolism; Binding Sites; Cell Line; Genes, Reporter; Humans; Ligands; Luciferases - genetics; Luciferases - metabolism; Models, Biological; Mutation; Original Paper; PDZ Domains; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Sequence Deletion; Signal Transduction; Transcription, Genetic; Transfection; β-Catenin; Erbin; PDZ domain; Wnt pathway; Splice variants; T cell factor
• ISSN: 0014-312X; 1421-9921
• DOI: 10.1159/000148241

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 β-catenin as a ligand of the PDZ domain of erbin. Here we demonstrate that erbin acts as a negative regulator of the β-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 β-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 β-catenin-regulated gene expression.