Integrin αvβ3 is a pleiotrophin receptor required for pleiotrophin‐induced endothelial cell migration through receptor protein tyrosine phosphatase β/ζ

C Mikelis, E Sfaelou, M Koutsioumpa… - The FASEB …, 2009 - Wiley Online Library
C Mikelis, E Sfaelou, M Koutsioumpa, N Kieffer, E Papadimitriou
The FASEB Journal, 2009Wiley Online Library
We have previously shown that the angiogenic growth factor pleiotrophin (PTN) induces
migration of endothelial cells through binding to its receptor protein tyrosine phosphatase
β/£(RPTPβ/ζ). In this study, we show that a monoclonal antibody against αvβ3 but not α5β1
integrin abolished PTN‐induced human endothelial cell migration in a concentration‐
dependent manner. Integrin αvβ3 was found to directly interact with PTN in an RGD‐
independent manner, whereas a synthetic peptide corresponding to the specificity loop of …
We have previously shown that the angiogenic growth factor pleiotrophin (PTN) induces migration of endothelial cells through binding to its receptor protein tyrosine phosphatase β/£ (RPTPβ/ζ). In this study, we show that a monoclonal antibody against αvβ3 but not α5β1 integrin abolished PTN‐induced human endothelial cell migration in a concentration‐dependent manner. Integrin αvβ3 was found to directly interact with PTN in an RGD‐independent manner, whereas a synthetic peptide corresponding to the specificity loop of the α3 integrin extracellular domain (177CYD‐ MKTTC184) inhibited PTN‐αvβ3 interaction and totally abolished PTN‐induced endothelial cell migration. Interestingly, αvβ3 was also found to directly interact with RPTPβ/ζ, and PTN‐induced Y773 phosphorylation of β3 integrin was dependent on both RPTPβ/ζ and the downstream c‐src kinase activation. Midkine was found to interact with RPTPβ/ζ, but not with αvβ3, 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 RPTPP/ζ but do not express αvβ3, while it stimulated migration of U87MG cells that express αvβ3 on their cell membrane. Overexpression or down‐regulation of β3 stimulated or abolished, respectively, the effect of PTN on cell migration. Collectively, these data suggest that αvβ3 is a key molecule that determines the stimulatory or inhibitory effect of PTN on cell migration.— Mikelis, C., Sfaelou, E., Koutsioumpa, M., Kieffer, N., Papadimitriou, E. Integrin ovP3 is a pleiotrophin receptor required for pleiotrophin‐induced endothelial cell migration through receptor protein tyrosine phosphatase P/£. FASEBJ. 23, 1459–1469 (2009)
Wiley Online Library