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

Stefanie Lapetina, Christopher C. Mader, Kazuya Machida, Bruce J. Mayer, Anthony J. Koleske

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)503-519
Number of pages17
JournalJournal of Cell Biology
Volume185
Issue number3
DOIs
StatePublished - 4 May 2009
Externally publishedYes

Funding

FundersFunder number
National Institute of Mental HealthR21MH077306
National Cancer InstituteR01CA082258
National Institute of Neurological Disorders and StrokeR01NS039475

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