Document Detail

The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation.
MedLine Citation:
PMID:  14709717     Owner:  NLM     Status:  MEDLINE    
The receptor protein tyrosine phosphatase density-enhanced phosphatase-1 (DEP-1) has been implicated in aberrant cancer cell growth and immune cell function, however, its function within cells has yet to be properly elucidated. To investigate the cellular function of DEP-1, stable cell lines inducibly expressing DEP-1 were generated. Induction of DEP-1 expression was found to decrease PDGF-stimulated tyrosine phosphorylation of a number of cellular proteins including the PDGF receptor, and to inhibit growth factor-stimulated phosphorylation of components of the MAPK pathway, indicating that DEP-1 antagonised PDGF receptor signalling. This was supported by data showing that DEP-1 expression resulted in a reduction in cell proliferation. DEP-1-expressing cells had fewer actin-containing microfilament bundles, reduced vinculin and paxillin-containing adhesion plaques, and were defective in interactions with fibronectin. Defective cell-substratum adhesion correlated with lack of activation of FAK in DEP-1-expressing cells. Time-lapse interference reflection microscopy of live cells revealed that although small focal contacts at the leading edge were generated in DEP-1-expressing cells, they failed to mature into stable focal adhesions, as found in control cells. Further motility analysis revealed that DEP-1-expressing cells retained limited random motility, but showed no chemotaxis towards a gradient of PDGF. In addition, cell-cell contacts were disrupted, with a change in the localisation of cadherin from discrete areas of cell-cell contact to large areas of membrane interaction, and there was a parallel redistribution of beta-catenin. These results demonstrate that DEP-1 is a negative regulator of cell proliferation, cell-substratum contacts, motility and chemotaxis in fibroblasts.
Stuart Kellie; Graham Craggs; Ian N Bird; Gareth E Jones
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-01-06
Journal Detail:
Title:  Journal of cell science     Volume:  117     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-19     Completed Date:  2004-09-29     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  609-18     Citation Subset:  IM    
School of Molecular and Microbial Sciences, Institute for Molecular Bioscience and CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane, QLD 4072, Australia.
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MeSH Terms
3T3 Cells
Cell Adhesion / drug effects
Cell Communication / physiology
Cell Division / drug effects
Cloning, Molecular
Cytoskeleton / drug effects,  metabolism*
Fibroblasts / cytology,  metabolism
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Focal Adhesions / physiology
Gene Expression Regulation, Enzymologic
Growth Substances / metabolism
Protein Phosphatase 1
Protein Tyrosine Phosphatases / genetics*,  metabolism,  pharmacology*
Protein-Tyrosine Kinases / metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 3
Recombinant Proteins / genetics,  metabolism,  pharmacology
Signal Transduction / physiology
Reg. No./Substance:
0/Growth Substances; 0/Recombinant Proteins; EC Adhesion Kinase 1; EC Kinases; EC Adhesion Protein-Tyrosine Kinases; EC protein, human; EC protein, mouse; EC Phosphatase 1; EC protein, human; EC Tyrosine Phosphatases; EC protein, mouse; EC Protein Tyrosine Phosphatases, Class 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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