Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 18, Pages 3071-3082Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.031575
Keywords
Abl PxxP motifs; Crk; Nck; filopodium and lamellipodium; cell spreading
Categories
Funding
- National Institutes of Health [CA82258]
- American Heart Association
- Academy of Finland
- Sigrid Juselius Foundation
- Helsinki University Hospital
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The dynamic reorganization of actin structures helps to mediate the interaction of cells with their environment. The Abl nonreceptor 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.
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