| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
The action mechanism by which the fibronectin-derived antiadhesive peptide (FNIII14) A membrane receptor mediating the biological effects of was investigated. Results obtained in this study are as follows.
1) Peptide FNIII14 suppersses not only the integrin-mediated cell adhesion but apoptosis induced by a tyrosine phosphatase inhibitor, phenylarsine oxide, through negatively regulating protein tyrosine phosphorylation of focal adhesion proteins including p125FAK.
2) Peptide FNIII14 can induce to transfer the β1 integrin conformation to an inactive form.
3) Antiadhesive response of cells to peptide FNIII14 is in parallel with the presence of a specific binding protein for FNIII14 (p55) on cell membrane, indicating that p55 could function as a specific mediator for FNIII.
4) p55, which was purified by immunoaffinity chromatography using mAb to p55, has an IgV domain in its N-terminal extracellular region.
During the investigation, we also obtained the following results.
1) The antiadhesive site, which is buried within the tertiary structure in plasma fibronectin, could be exposed from fibronectin by interaction with heparin and by proteolysis with MMP-2.
2) Peptide FNIII14 is capable of suppressing myofibroblastic conversion of rat hepatic stellate cells, leading the speculation that FNIII14 may be applicable to drug for anti-hepatic fibrosis.
3) FNIII14 suppresses PDGF-induced proliferation of NIH/3T3 cells through abrogating tyrosine phosphorylation of ERK-1 and 2.
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