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The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell-matrix adhesion
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
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2003 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 22, no 27, 4175-4185 p.Article in journal (Refereed) Published
Abstract [en]

Density-enhanced protein-tyrosine phosphatase-1 (DEP-1 also CD148) is a transmembrane molecule with a single intracellular PTP domain. It has recently been proposed to function as a tumor suppressor. We have previously shown that DEP-1 dephosphorylates the activated platelet-derived growth factor (PDGF) beta-receptor in a site-selective manner (Kovalenko et al. (2000). J. Biol. Chem. 275, 16219-16226). We analysed cell lines with inducible DEP-1 expression for cellular functions of DEP-1. Several aspects of PDGFbeta-receptor signaling were negatively affected by DEP-1 expression. These include PDGF-stimulated activation of inositol trisphosphate formation, Erk1/2, p21Ras, and Src. Activation of receptor-associated phosphoinositide-3 kinase activity and of Akt/PKB were weakly attenuated at early time points of stimulation. Inhibition of PDGF-stimulated signaling depended on DEP-1 catalytic activity. Importantly, DEP-1 inhibited PDGF-stimulated cell migration. The catalytically inactive DEP-1 C1239S variant enhanced cell migration and PDGF-stimulated Erk1/2 activation, suggesting a dominant negative interference with endogenous DEP-1. In contrast to cell migration, cell-substrate adhesion was promoted by active DEP-1 and delayed or suppressed by DEP-1 C1239S, correlating with positive effects of DEP-1 on adhesion-stimulated Src kinase. We propose that negative regulation of growth-factor stimulated cell migration and promotion of cell-matrix adhesion may be related to the function of DEP-1 as tumor suppressor.

Place, publisher, year, edition, pages
2003. Vol. 22, no 27, 4175-4185 p.
Keyword [en]
1-Phosphatidylinositol 3-Kinase/metabolism, 3T3 Cells, Animals, Cell Adhesion, Cell Division, Cell Movement, Dose-Response Relationship; Drug, Enzyme Activation, Gene Expression Regulation, Genetic Vectors, Growth Substances/*metabolism, Immunoblotting, Inositol 1;4;5-Trisphosphate/metabolism, Mice, Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases/metabolism, Mutation, Platelet-Derived Growth Factor/metabolism, Protein-Serine-Threonine Kinases, Protein-Tyrosine-Phosphatase/metabolism/*physiology, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-akt, Signal Transduction, Time Factors, Transfection, ras Proteins/metabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-10674DOI: 10.1038/sj.onc.1206652PubMedID: 12833140OAI: oai:DiVA.org:uu-10674DiVA: diva2:38442
Available from: 2007-04-18 Created: 2007-04-18 Last updated: 2013-11-05Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=12833140&dopt=Citation
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