Fibronectin type I repeat is a nonactivating ligand for EphA1 and inhibits ATF3-dependent angiogenesis |
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Authors: | Masuda Junko Usui Ryosuke Maru Yoshiro |
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Institution: | Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. |
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Abstract: | 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. |
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