CDB25:0004139 PTN — ITGAV

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

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

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009; PubMed, Homo sapiens PTN — Homo sapiens ITGAV
ABSTRACT: 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.
Basic Information on PTN
Ligand Name: pleiotrophin
Other Symbols: NEGF1, HBNF, HBGF8
Ligand Location: secreted based on hpa, perplexity, uniprot
HGNC Gene Symbol Report: PTN
GeneCards: PTN
HGNC Gene Group: Receptor ligands
Basic Information on ITGAV
Receptor Name: integrin subunit alpha V
Other Symbols: VNRA, MSK8, VTNR, CD51
Receptor Location: cell membrane based on perplexity, uniprot
HGNC Gene Symbol Report: ITGAV
GeneCards: ITGAV
HGNC Gene Group: CD molecules, Integrins