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Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion

¹ Department of Molecular Biophysics and Biochemistry, ² Department of Cell Biology, ³ Department of Neurobiology, and ⁴ Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520
⁵ Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030

Correspondence to Anthony J. Koleske: anthony.koleske{at}yale.edu

The molecular mechanisms by which the Abelson (Abl) or Abl-related gene (Arg) kinases interface with the actin polymerization machinery to promote cell edge protrusions during cell–matrix adhesion are unclear. In this study, we show that interactions between Arg and the Arp2/3 complex regulator cortactin are essential to mediate actin-based cell edge protrusion during fibroblast adhesion to fibronectin. Arg-deficient and cortactin knockdown fibroblasts exhibit similar defects in adhesion-dependent cell edge protrusion, which can be restored via reexpression of Arg and cortactin. Arg interacts with cortactin via both binding and catalytic events. The cortactin Src homology (SH) 3 domain binds to a Pro-rich motif in the Arg C terminus. Arg mediates adhesion-dependent phosphorylation of cortactin, creating an additional binding site for the Arg SH2 domain. Mutation of residues that mediate Arg–cortactin interactions abrogate the abilities of both proteins to support protrusions, and the Nck adapter, which binds phosphocortactin, is also required. These results demonstrate that interactions between Arg, cortactin, and Nck1 are critical to promote adhesion-dependent cell edge protrusions.

© 2009 Lapetina et al.
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This article has been cited by other articles:

• Bradley, W. D., Koleske, A. J. (2009). Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts. J. Cell Sci. 122: 3441-3454 [Abstract] [Full Text]  

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