title: Identification of an active site on the laminin alpha4 chain globular domain that binds to alphavbeta3 integrin and promotes angiogenesis.
abstract: Angiogenesis is important for wound healing, tumor growth, and metastasis. The laminin alpha4 chain, a component of laminin-8 and -9, is expressed in endothelial cell basement membranes. It mediates endothelial cell adhesion by binding with its receptors such as alphavbeta3 integrin and participates in new blood vessel formation. In this study, we found the recombinant laminin alpha4LG modules (rLG1-3, rLG1, and rLG2) mediate HUVECs adhesion. The attachment of HUVECs to the rLG2 was specifically inhibited by a function-blocking monoclonal antibody LM609 specific for alphavbeta3 integrin. Using deletion mutants of the alpha4LG2 revealed the HUVECs-adhesion site is located in amino acids 1121-1139. A synthetic G(1121-1139) peptide could be attached by HUVECs at same efficiency with the rLG2 and promoted angiogenesis in CAM. In conclusion, we have identified a new alphavbeta3 integrin-interacting peptide within laminin alpha4 G domain. This suggests that G(1121-1139) peptide-containing proteins may perform their biological functions by interacting with alphavbeta3 integrin.
authors.affiliation: Faculty of Basic Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Jiqin
authors.initials: J
authors.lastname: Lian
authors.forename: Xufang
authors.initials: X
authors.lastname: Dai
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Fengtian
authors.initials: F
authors.lastname: He
mesh_terms: D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry* / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry* / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D039302:Integrin alphaVbeta3; C501369:LAMA4 protein, human; D007797:Laminin