uPAR promotes formation of the p130Cas-Crk complex to activate Rac through DOCK180.

The Journal of Cell Biology
Harvey W SmithChristopher J Marshall

Abstract

The urokinase-type plasminogen activator receptor (uPAR) drives tumor cell membrane protrusion and motility through activation of Rac; however, the pathway leading from uPAR to Rac activation has not been described. In this study we identify DOCK180 as the guanine nucleotide exchange factor acting downstream of uPAR. We show that uPAR cooperates with integrin complexes containing beta(3) integrin to drive formation of the p130Cas-CrkII signaling complex and activation of Rac, resulting in a Rac-driven elongated-mesenchymal morphology, cell motility, and invasion. Our findings identify a signaling pathway underlying the morphological changes and increased cell motility associated with uPAR expression.

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Methods Mentioned

BETA
GTPase
coimmunoprecipitation
GTPases
nucleotide exchange
pull-down
pull down
transfection
immunoprecipitation
flow cytometry
transfections

Software Mentioned

Simple PCI
Photoshop
Excel
iMovie HD
Premiere
Adobe
LaserSharp
Simple PCI AIC

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