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Integrin α v β 3 is a pleiotrophin receptor required for pleiotrophin‐induced endothelial cell migration through receptor protein tyrosine phosphatase β/ζ
Author(s) -
Mikelis Constantinos,
Sfaelou Evanthia,
Koutsioumpa Marina,
Kieffer Nelly,
Papadimitriou Evangelia
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-117564
Subject(s) - pleiotrophin , midkine , integrin , chemistry , tyrosine phosphorylation , microbiology and biotechnology , protein tyrosine phosphatase , phosphorylation , cell migration , receptor , biology , growth factor , cell , biochemistry
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 α v β 3 but not α 5 β 1 integrin abolished PTN‐induced human endothelial cell migration in a concentration‐dependent manner. Integrin α v β 3 was found to directly interact with PTN in an RGD‐independent manner, whereas a synthetic peptide corresponding to the specificity loop of the α 3 integrin extracellular domain ( 177 CYD‐ MKTTC 184 ) inhibited PTN‐α v β 3 interaction and totally abolished PTN‐induced endothelial cell migration. Interestingly, α v β 3 was also found to directly interact with RPTPβ/ζ, and PTN‐induced Y773 phosphorylation of β 3 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 α v β 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 RPTPP/ζ but do not express α v β 3 , while it stimulated migration of U87MG cells that express α v β 3 on their cell membrane. Overexpression or down‐regulation of β 3 stimulated or abolished, respectively, the effect of PTN on cell migration. Collectively, these data suggest that α v β 3 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)