title: Antiadhesive sites present in the fibronectin type III-like repeats of human plasma fibronectin.
abstract: We have found that fibronectin (FN) has a functional cryptic site opposing cell adhesion to extracellular matrix (ECM): a synthetic FN peptide derived from the 14th FN type III-like (FN-III) repeat, termed peptide FNIII14, inhibits cell adhesion to the FN without binding to beta1 integrins. This antiadhesive activity of peptide FNIII14 depends on its C-terminal amino acid sequence YTIYVIAL. A 50-kDa membrane protein (p50) has been detected as a specific binding protein of peptide FNIII14. Here we showed that antiadhesive activity of peptide FNIII14 was depedent upon the presence of p50 on cell surfaces. Furthermore, we found that there exists a sequence, analogous to the YTIYVIAL, in the 10th FN-III repeat of the FN molecule and that a FN peptide containing this analogous sequence, termed peptide FNIII10, inhibited cell adhesion to the FN. Peptide FNIII10 appeared to share p50 with peptide FNIII14 in expressing the antiadhesive activity. As a physiological consequence of decreased adhesion, peptides FNIII10 and FNIII14 accelerated the anoikis-like apoptosis of normal fibroblasts by down-regulating Bcl-2 expression through blocking the FAK/PI3K/Akt signaling pathway. Thus, the YTIYVIAL-related sequences of the FN molecule may be involved in cell regulation by modulating negatively cell adhesion to the ECM, in which p50 probably serves as a membrane receptor.
authors.affiliation: Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Miura
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Kamiya
authors.forename: Yohei
authors.initials: Y
authors.lastname: Saito
authors.forename: Seiki
authors.initials: S
authors.lastname: Wada
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayashi
authors.forename: Junichi
authors.initials: J
authors.lastname: Taira
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kodama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yajima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ueki
authors.forename: Fumio
authors.initials: F
authors.lastname: Fukai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D011485:Protein Binding; D013379:Substrate Specificity; D020079:Terminal Repeat Sequences
chemical_list: D005353:Fibronectins; D016023:Integrins; D008565:Membrane Proteins; D010446:Peptide Fragments; C501364:fibronectin type III like peptide, human