Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling.

Authors: Abassi, YA  Vuori, K 
Citation: Abassi YA and Vuori K, EMBO J 2002 Sep 2;21(17):4571-82.
Pubmed: (View Article at PubMed) PMID:12198159

The adaptor protein CrkII plays a central role in signal transduction cascades downstream of a number of different stimuli. We and others have previously shown that CrkII mediates attachment-induced JNK activation, membrane ruffling and cell motility in a Rac-dependent manner. We report here that cell attachment leads to tyrosine phosphorylation of CrkII on Y221, and that CrkII-Y221F mutant demonstrates enhanced association with the Crk-binding partners C3G and paxillin. Despite this enhanced signaling complex formation, CrkII-Y221F fails to induce JNK and PAK activation, membrane ruffling and cell migration, suggesting that it is defective in activating Rac signaling. Wild-type CrkII has no effect on adhesion-induced GTP loading of Rac, but its expression results in enhanced membrane localization of Rac, which is known to be required for Rac signaling. In contrast, CrkII-Y221F is deficient in enhancing membrane localization of Rac. Mutations in Rac and CrkII-Y221F that force membrane targeting of these molecules restore Rac signaling in adherent cells. Together, these results indicate that the Y221 site in CrkII regulates Rac membrane translocation upon cell adhesion, which is necessary for activation of downstream Rac signaling pathways.


Gene Ontology Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 1298803
Created: 2004-06-01
Species: All species
Last Modified: 2006-04-25
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.