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PMID:14709717

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Citation

Kellie, S, Craggs, G, Bird, IN and Jones, GE (2004) The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation. J. Cell. Sci. 117:609-18

Abstract

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.

Links

PubMed Online version:10.1242/jcs.00879

Keywords

3T3 Cells; Animals; Cell Adhesion/drug effects; Cell Communication/physiology; Cell Division/drug effects; Cloning, Molecular; Cytoskeleton/drug effects; Cytoskeleton/metabolism; Fibroblasts/cytology; Fibroblasts/metabolism; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions/physiology; Gene Expression Regulation, Enzymologic; Growth Substances/metabolism; Humans; Mice; Protein Phosphatase 1; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/metabolism; Protein Tyrosine Phosphatases/pharmacology; Protein-Tyrosine Kinases/metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 3; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Recombinant Proteins/pharmacology; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PTPRJ

involved_in

GO:0050918: positive chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PTPRJ

involved_in

GO:0030308: negative regulation of cell growth

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PTPRJ

involved_in

GO:0010642: negative regulation of platelet-derived growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PTPRJ

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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