Abstract
The expression of the Syk protein tyrosine kinase in breast cancer cells is inversely correlated with invasive growth and metastasis. The expression of Syk inhibits cell motility while supporting the formation of cell clusters by enhancing cell-cell contacts and promoting the redistribution of the adhesion proteins cortactin and vinculin to these contacts. Syk associates physically with cortactin and catalyzes its phosphorylation on tyrosine. The clustering of integrins leads to the phosphorylation of Syk and of numerous cellular proteins in a manner dependent on the activity of the kinase and on the presence of tyrosine 342 located in the linker B region. The ability of Syk to participate in integrin-mediated protein tyrosine phosphorylation correlates well with its ability to inhibit cell motility.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Binding Sites
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Blotting, Western
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Breast Neoplasms / enzymology
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Breast Neoplasms / pathology
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Breast Neoplasms / physiopathology
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Cell Adhesion / physiology
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Cell Communication / physiology*
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Cell Line, Tumor
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Cell Movement / physiology*
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Cell Nucleus / metabolism
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Cortactin / metabolism
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Cross-Linking Reagents / chemistry
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Cytoplasm / metabolism
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Enzyme Activation
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Female
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Integrins / chemistry
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Integrins / metabolism
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Microscopy, Fluorescence
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Phosphorylation
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Protein Binding
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Protein Transport
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Syk Kinase
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Transfection
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Tyrosine / metabolism
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Vinculin / metabolism
Substances
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Cortactin
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Cross-Linking Reagents
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Integrins
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Intracellular Signaling Peptides and Proteins
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Recombinant Fusion Proteins
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Vinculin
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Green Fluorescent Proteins
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Tyrosine
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase