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Identification of p130Cas as a Mediator of Focal Adhesion Kinase–promoted Cell Migration
- Source :
- The Journal of Cell Biology
- Publication Year :
- 1998
- Publisher :
- The Rockefeller University Press, 1998.
-
Abstract
- Previously we have demonstrated that focal adhesion kinase (FAK)-promoted migration on fibronectin (FN) by its overexpression in CHO cells is dependent on FAK autophosphorylation at Y397 and subsequent binding of Src to this site. In this report, we have examined the role of FAK association with Grb2 and p130Cas, two downstream events of the FAK/Src complex that could mediate integrin-stimulated activation of extracellular signal-regulated kinases (Erks). We show that a Y925F FAK mutant was able to promote cell migration as efficiently as FAK and that the transfected FAK demonstrated no detectable association with Grb2 in CHO cells. In contrast, cells expressing a FAK P712/715A mutant demonstrated a level of migration comparable to that of control cells. This mutation did not affect FAK kinase activity, autophosphorylation, or Src association but did significantly reduce p130Cas association with FAK. Furthermore, FAK expression in CHO cells increased tyrosine phosphorylation of p130Cas and its subsequent binding to several SH2 domains, which depended on both the p130Cas binding site and the Src binding site. However, we did not detect increased activation of Erks in cells expressing FAK, and the MEK inhibitor PD98059 did not decrease FAK-promoted cell migration. Finally, we show that coexpression of p130Cas further increased cell migration on FN and coexpression of the p130Cas SH3 domain alone functioned as a dominant negative mutant and decreased cell migration. Together, these results demonstrate that p130Cas, but not Grb2, is a mediator of FAK-promoted cell migration and suggest that FAK/ p130Cas complex targets downstream pathways other than Erks in mediating FAK-promoted cell migration.
- Subjects :
- Recombinant Fusion Proteins
Integrin
CHO Cells
Biology
Transfection
Polymerase Chain Reaction
SH3 domain
Article
Focal adhesion
src Homology Domains
03 medical and health sciences
0302 clinical medicine
Cricetinae
Animals
Point Mutation
Kinase activity
030304 developmental biology
Glutathione Transferase
0303 health sciences
Binding Sites
Retinoblastoma-Like Protein p130
Cell adhesion molecule
Chemotaxis
Autophosphorylation
Proteins
Cell migration
Cell Biology
Protein-Tyrosine Kinases
Phosphoproteins
Molecular biology
Cell biology
Crk-Associated Substrate Protein
030220 oncology & carcinogenesis
Focal Adhesion Protein-Tyrosine Kinases
biology.protein
Mutagenesis, Site-Directed
biological phenomena, cell phenomena, and immunity
Cell Adhesion Molecules
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 140
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....6e439fafa182b0c5bba54bf502c3a79b