Fibronectin type I repeat is a nonactivating ligand for EphA1 and inhibits ATF3-dependent angiogenesis.
ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. Although tyrosine kinase activation of EphA1 was dispensable, binding of EphA1 to fibronectin through its type I repeat played an essential role in the angiogenesis. Recombinant proteins containing fibronectin 10th to 12th type I repeat (I 10-12) but not I 12 could inhibit the angiogenesis in vitro by competitively targeting EphA1 with the full-length fibronectin. However, I 12 acquired a higher affinity toward EphA2 with K(d) 18 nm and inhibited vascular endothelial growth factor-dependent angiogenic invasion in a Matrigel plug assay.
Masuda
Junko
J
Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Usui
Ryosuke
R
Maru
Yoshiro
Y
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004317:Doxorubicin / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D036082:Receptor, EphA1 / Q000235:genetics / Q000378:metabolism*
D051700:Activating Transcription Factor 3; D005353:Fibronectins; D008024:Ligands; D004317:Doxorubicin; D036082:Receptor, EphA1