Integrin alpha(v)beta(3) is a pleiotrophin receptor required for pleiotrophin-induced endothelial cell migration through receptor protein tyrosine phosphatase beta/zeta

FASEB J. 2009 May;23(5):1459-69. doi: 10.1096/fj.08-117564. Epub 2009 Jan 13.


We have previously shown that the angiogenic growth factor pleiotrophin (PTN) induces migration of endothelial cells through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta). In this study, we show that a monoclonal antibody against alpha(nu)beta(3) but not alpha(5)beta(1) integrin abolished PTN-induced human endothelial cell migration in a concentration-dependent manner. Integrin alpha(nu)beta(3) was found to directly interact with PTN in an RGD-independent manner, whereas a synthetic peptide corresponding to the specificity loop of the beta(3) integrin extracellular domain ((177)CYDMKTTC(184)) inhibited PTN-alpha(nu)beta(3) interaction and totally abolished PTN-induced endothelial cell migration. Interestingly, alpha(nu)beta(3) was also found to directly interact with RPTPbeta/zeta, and PTN-induced Y773 phosphorylation of beta(3) integrin was dependent on both RPTPbeta/zeta and the downstream c-src kinase activation. Midkine was found to interact with RPTPbeta/zeta, but not with alpha(nu)beta(3), and caused a small but statistically significant decrease in cell migration. In the same line, PTN decreased migration of different glioma cell lines that express RPTPbeta/zeta but do not express alpha(nu)beta(3), while it stimulated migration of U87MG cells that express alpha(nu)beta(3) on their cell membrane. Overexpression or down-regulation of beta(3) stimulated or abolished, respectively, the effect of PTN on cell migration. Collectively, these data suggest that alpha(nu)beta(3) is a key molecule that determines the stimulatory or inhibitory effect of PTN on cell migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / physiology*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cytokines / physiology*
  • Humans
  • Integrin alphaVbeta3 / physiology*
  • Midkine
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5
  • src-Family Kinases / metabolism


  • Carrier Proteins
  • Cytokines
  • Integrin alphaVbeta3
  • pleiotrophin
  • Midkine
  • src-Family Kinases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5