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Vol. 15, Issue 1, 397-406, January 2004
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* Humangenetik fuer Biologen, Johann Wolfgang Goethe-Universität, D-60054 Frankfurt, Germany;
Bürgerhospital Frankfurt, Section of Gynecological Endocrinology and Fertility Surgery, D-60318 Frankfurt, Germany
Submitted May 7, 2003;
Revised September 1, 2003;
Accepted September 9, 2003
Monitoring Editor: Mary Beckerle
While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative 411-amino acid integral membrane protein that we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides that labeled a protein of
48 kDa in extracts of shrew-1 mRNA-positive tissue and also detected ectopically expressed shrew-1. Expression of epitope-tagged shrew-1 in epithelial cells and analysis by surface biotinylation and immunoblots demonstrated that shrew-1 is indeed a transmembrane protein. Shrew-1 is able to target to E-cadherin-mediated adherens junctions and interact with the E-cadherincatenin complex in polarized MCF7 and Madin-Darby canine kidney cells, but not with the N-cadherincatenin complex in nonpolarized epithelial cells. Direct interaction of shrew-1 with
-catenin in in vitro pull-down assay suggests that
-catenin might be one of the proteins that targets and/or retains shrew-1 in the adherens junctions. Interestingly, shrew-1 was partially translocated in response to scatter factor (ligand of receptor tyrosine kinase c-met) from the plasma membrane to the cytoplasm where it still colocalized with endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of adherens junctions, interacting with E-cadherin
-catenin complexes in polarized epithelial cells.
Corresponding author. E-mail address: starzinski-powitz{at}em.uni-frankfurt.de.
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