Identification of the alphavbeta3 integrin-interacting motif of betaig-h3 and its anti-angiogenic effect.
betaig-h3 is an extracellular matrix protein that mediates adhesion and migration of several cell types through interaction with integrins. In the present study, we tested whether betaig-h3 mediates endothelial cell adhesion and migration, thereby regulating angiogenesis. In this study, we demonstrate that not only betaig-h3 itself but also all four fas-1 domains of betaig-h3 mediate endothelial cell adhesion and migration through interaction with the alphavbeta3 integrin. We found that the alphavbeta3 integrin-interacting motif of the four fas-1 domains of betaig-h3 is the same YH motif that we reported previously to interact with alphavbeta5 integrin. The YH peptide inhibited endothelial cell adhesion and migration in a dose-dependent manner. We demonstrate that the YH peptide has anti-angiogenic activity in vitro and in vivo using an endothelial cell tube formation assay and a Matrigel plug assay, respectively. Our results reveal that betaig-h3 bears alphavbeta3 integrin-interacting motifs that mediate endothelial cell adhesion and migration and, therefore, may regulate angiogenesis.
Nam
Ju-Ock
JO
Cell and Matrix Biology National Research Laboratory, Department of Biochemistry, Kyungpook National University School of Medicine, Taegu 700-422, Korea.
Kim
Jung-Eun
JE
Jeong
Ha-Won
HW
Lee
Sung-Jin
SJ
Lee
Byung-Heon
BH
Choi
Je-Yong
JY
Park
Rang-Woon
RW
Park
Jae Yong
JY
Kim
In-San
IS
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology; D016326:Extracellular Matrix Proteins; D005434:Flow Cytometry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry*; D007797:Laminin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D016212:Transforming Growth Factor beta; D014471:Umbilical Veins / Q000166:cytology; D000099222:betaIG-H3 Protein
D003094:Collagen; D004247:DNA; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D039302:Integrin alphaVbeta3; D007797:Laminin; D009363:Neoplasm Proteins; D010455:Peptides; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C059485:matrigel