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PMID:15728191

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Citation

Pratt, SJ, Epple, H, Ward, M, Feng, Y, Braga, VM and Longmore, GD (2005) The LIM protein Ajuba influences p130Cas localization and Rac1 activity during cell migration. J. Cell Biol. 168:813-24

Abstract

Cell migration requires extension of lamellipodia that are stabilized by formation of adhesive complexes at the leading edge. Both processes are regulated by signaling proteins recruited to nascent adhesive sites that lead to activation of Rho GTPases. The Ajuba/Zyxin family of LIM proteins are components of cellular adhesive complexes. We show that cells from Ajuba null mice are inhibited in their migration, without associated abnormality in adhesion to extracellular matrix proteins, cell spreading, or integrin activation. Lamellipodia production, or function, is defective and there is a selective reduction in the level and tyrosine phosphorylation of FAK, p130Cas, Crk, and Dock180 at nascent focal complexes. In response to migratory cues Rac activation is blunted in Ajuba null cells, as detected biochemically and by FRET analysis. Ajuba associates with the focal adhesion-targeting domain of p130Cas, and rescue experiments suggest that Ajuba acts upstream of p130Cas to localize p130Cas to nascent adhesive sites in migrating cells thereby leading to the activation of Rac.

Links

PubMed PMC2171823 Online version:10.1083/jcb.200406083

Keywords

Animals; Cell Movement/physiology; Crk-Associated Substrate Protein; Cytoskeletal Proteins/metabolism; Extracellular Matrix Proteins/metabolism; Fibroblasts/physiology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Homeodomain Proteins/metabolism; Mice; Paxillin; Phosphoproteins/metabolism; Protein-Tyrosine Kinases/metabolism; Proteins/metabolism; Pseudopodia/metabolism; Retinoblastoma-Like Protein p130; Time Factors; rac1 GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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