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PMID:11084024
| Citation |
Bourguignon, LY, Zhu, H, Shao, L and Chen, YW (2001) CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. J. Biol. Chem. 276:7327-36 |
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| Abstract |
In this study we have demonstrated that both CD44 (the hyaluronan (HA) receptor) and c-Src kinase are expressed in human ovarian tumor cells (SK-OV-3.ipl cell line), and that these two proteins are physically associated as a complex in vivo. Using a recombinant cytoplasmic domain of CD44 and an in vitro binding assay, we have detected a specific interaction between CD44 and c-Src kinase. Furthermore, the binding of HA to SK-OV-3.ipl cells promotes c-Src kinase recruitment to CD44 and stimulates c-Src kinase activity, which, in turn, increases tyrosine phosphorylation of the cytoskeletal protein, cortactin. Subsequently, tyrosine phosphorylation of cortactin attenuates its ability to cross-link filamentous actin in vitro. In addition, transfection of SK-OV-3.ipl cells with a dominant active form of c-Src (Y527F)cDNA promotes CD44 and c-Src association with cortactin in membrane projections, and stimulates HA-dependent/CD44-specific ovarian tumor cell migration. Finally, overexpression of a dominant-negative mutant of c-Src kinase (K295R) in SK-OV-3.ipl cells impairs the tumor cell-specific phenotype. Taken together, these findings strongly suggest that CD44 interaction with c-Src kinase plays a pivotal role in initiating cortactin-regulated cytoskeleton function and HA-dependent tumor cell migration, which may be required for human ovarian cancer progression. |
| Links |
PubMed Online version:10.1074/jbc.M006498200 |
| Keywords |
Animals; Antigens, CD44/chemistry; Antigens, CD44/genetics; Antigens, CD44/metabolism; Cell Movement; Cloning, Molecular; Cortactin; Cytoskeleton/metabolism; DNA, Complementary/metabolism; Female; Genes, Dominant; Humans; Hyaluronic Acid/pharmacology; Immunoblotting; Microfilament Proteins/metabolism; Microscopy, Fluorescence; Mutation; Ovarian Neoplasms/metabolism; Phenotype; Phosphorylation; Plasmids/metabolism; Precipitin Tests; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins pp60(c-src)/metabolism; Rats; Recombinant Proteins/metabolism; Time Factors; Transfection; Tumor Cells, Cultured; Tyrosine/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0033674: positive regulation of kinase activity |
ECO:0000314: |
P |
Figure 3 shows kinase activity when HA binds to CD44. This shows a correlation between receptor activity of CD44 and its regulation of src kinase activity |
complete | ||||
|
involved_in |
GO:0033674: positive regulation of kinase activity |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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