A critical role for cortactin phosphorylation by Abl-family kinases in PDGF-induced dorsal-wave formation

Curr Biol. 2007 Mar 6;17(5):445-51. doi: 10.1016/j.cub.2007.01.057. Epub 2007 Feb 15.


Proper regulation of cell morphogenesis and migration by adhesion and growth-factor receptors requires Abl-family tyrosine kinases [1-3]. Several substrates of Abl-family kinase have been identified, but they are unlikely to mediate all of the downstream actions of these kinases on cytoskeletal structure. We used a human protein microarray to identify the actin-regulatory protein cortactin as a novel substrate of the Abl and Abl-related gene (Arg) nonreceptor tyrosine kinases. Cortactin stimulates cell motility [4-6], and its upregulation in several cancers correlates with poor prognosis [7]. Even though cortactin can be tyrosine phosphorylated by Src-family kinases in vitro [8], we show that Abl and Arg are more adept at binding and phosphorylating cortactin. Importantly, we demonstrate that platelet-derived growth-factor (PDGF)-induced cortactin phosphorylation on three tyrosine residues requires Abl or Arg. Cortactin triggers F-actin-dependent dorsal waves in fibroblasts after PDGF treatment and thus results in actin reorganization and lamellipodial protrusion [9]. We provide evidence that Abl/Arg-mediated phosphorylation of cortactin is required for this PDGF-induced dorsal-wave response. Our results reveal that Abl-family kinases target cortactin as an effector of cytoskeletal rearrangements in response to PDGF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3 Cells
  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Actins / metabolism
  • Animals
  • Cell Membrane / metabolism*
  • Cortactin / metabolism*
  • Dynamins / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • Phosphorylation
  • Platelet-Derived Growth Factor / metabolism
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein Array Analysis
  • Protein-Tyrosine Kinases / metabolism*


  • Actins
  • CTTN protein, human
  • Cortactin
  • Platelet-Derived Growth Factor
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases
  • Dynamins