Role of the protein tyrosine kinase Syk in regulating cell-cell adhesion and motility in breast cancer cells.
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.
Department of Medicinal Chemistry, Purdue University, Hansen Life Sciences Research Building, 201 South University Street, West Lafayette, IN 47907-2064, USA.
Xiaoying
X
Zhang
Ulka
U
Shrikhande
Bethany M
BM
Alicie
Qing
Q
Zhou
Robert L
RL
Geahlen
D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D051356:Cortactin / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000072377:Syk Kinase; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
D051356:Cortactin; D003432:Cross-Linking Reagents; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D016596:Vinculin; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase