The role of tyrosine phosphorylation of cortactin in the locomotion of endothelial cells

J Biol Chem. 1998 Oct 2;273(40):25770-6. doi: 10.1074/jbc.273.40.25770.


Cortactin, a filamentous actin cross-linking protein and a substrate of Src protein tyrosine kinase, is phosphorylated at tyrosine residues upon stimulation by extracellular signals. We have previously demonstrated that the filamentous actin cross-linking activity of cortactin is attenuated by Src (Huang, C., Ni, Y., Gao, Y., Haudenschild, C. C., and Zhan, X. (1997) J. Biol. Chem. 272, 13911-13915). In vitro, tyrosine phosphorylation of cortactin occurs specifically within the region between the proline-rich sequence and the Src homology 3 domain. Among the nine tyrosine residues in this region, mutations at Tyr421, Tyr466, and Tyr482 significantly reduced Src-meditated tyrosine phosphorylation both in vitro and in vivo. Ectopic expression of wild-type cortactin in ECV304, a spontaneously transformed human umbilical endothelial cell line, resulted in an enhanced cell migration. In contrast, overexpression of a cortactin mutant deficient in tyrosine phosphorylation impaired the migration of endothelial cells. These findings reveal an intracellular signaling mechanism whereby the motility of endothelial cells is regulated by a Src-mediated tyrosine phosphorylation of cortactin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Movement / physiology*
  • Cortactin
  • Endothelium, Vascular / physiology
  • Epitopes / immunology
  • Fluorescent Antibody Technique
  • Humans
  • Mice
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics
  • Molecular Sequence Data
  • Mutation / genetics
  • Phosphopeptides / chemistry
  • Phosphorylation
  • Phosphotyrosine / metabolism*
  • Sequence Analysis
  • Signal Transduction / physiology
  • src Homology Domains
  • src-Family Kinases / metabolism


  • Actins
  • CTTN protein, human
  • Cortactin
  • Cttn protein, mouse
  • Epitopes
  • Microfilament Proteins
  • Phosphopeptides
  • Phosphotyrosine
  • src-Family Kinases