Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Comments

J Cell Sci. Author manuscript; available in PMC Oct 27, 2009. Published in final edited form as: J Cell Sci. Sep 15, 2008; 121(Pt 18): 3071–3082. PMCID: PMC2768557 NIHMSID: NIHMS109333

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