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First published online September 3, 2008
doi: 10.1242/10.1242/jcs.031575
Research Article |
1 Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301 USA
2 Department of Virology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, FIN-00014, Finland
* Author for correspondence (e-mail: bmayer{at}neuron.uchc.edu)
Accepted 3 July 2008
The dynamic reorganization of actin structures helps to mediate the interaction of cells with their environment. The Abl non-receptor tyrosine kinase can modulate actin rearrangement during cell attachment. Here we report that the Abl PxxP motifs, which bind Src homology 3 (SH3) domains, are indispensable for the coordinated regulation of filopodium and focal adhesion formation and cell-spreading dynamics during attachment. Candidate Abl PxxP-motif-binding partners were identified by screening a comprehensive SH3-domain phage-display library. A combination of protein overexpression, silencing, pharmacological manipulation and mutational analysis demonstrated that the PxxP motifs of Abl exert their effects on actin organization by two distinct mechanisms, involving the inhibition of Crk signaling and the engagement of Nck. These results uncover a previously unappreciated role for Abl PxxP motifs in the regulation of cell spreading.
Key words: Abl PxxP motifs, Crk, Nck, Filopodium and lamellipodium, Cell spreading
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