Identification of a membrane receptor mediating the biological effects of the fibronectin-derivedantiadhesive peptide FNIII 14.

研究了纤维连接蛋白衍生的抗粘附肽（FNIII14） A膜受体介导生物效应的作用机制。本研究的结果如下：1)肽FNIII14不仅抑制整合素介导的细胞粘附，而且通过负调控p125FAK等局灶粘附蛋白的酪氨酸磷酸化，抑制酪氨酸磷酸酶抑制剂苯larsine oxide诱导的细胞凋亡。2)肽FNIII14可以诱导β1整合素构象转移到非活性形式。3)细胞对肽FNIII14的抗粘附反应与细胞膜上FNIII14的特异性结合蛋白（p55）的存在是平行的，这表明p55可以作为FNIII14的特异性介质。4)p55通过免疫亲和层析使用mAb对p55进行纯化，其n端胞外区具有IgV结构域。在调查过程中，我们还获得了以下结果。1)埋在血浆纤维连接蛋白三级结构内的抗粘附位点，可通过与肝素的相互作用和与mmp的蛋白水解而暴露于纤维连接蛋白。2.2)肽FNIII14能够抑制大鼠肝星状细胞的成肌纤维转化，推测FNIII14可能适用于抗肝纤维化药物。3) FNIII14通过消除ERK-1和2的酪氨酸磷酸化，抑制pdgf诱导的NIH/3T3细胞增殖。

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.