Naldini L, Weidner K M, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan R P, Hartmann G, Zarnegar R, Michalopoulos G K
Department of Biomedical Sciences and Oncology, University of Torino, School Medicine, Italy.
EMBO J. 1991 Oct;10(10):2867-78. doi: 10.1002/j.1460-2075.1991.tb07836.x.
Scatter Factor (SF) is a fibroblast-secreted protein which promotes motility and matrix invasion of epithelial cells. Hepatocyte Growth Factor (HGF) is a powerful mitogen for hepatocytes and other epithelial tissues. SF and HGF, purified according to their respective biological activities, were interchangeable and equally effective in assays for cell growth, motility and invasion. Both bound with identical affinities to the same sites in target cells. The receptor for SF and HGF was identified as the product of the MET oncogene by: (i) ligand binding and coprecipitation in immunocomplexes; (ii) chemical crosslinking to the Met beta subunit; (iii) transfer of binding activity in insect cells by a baculovirus carrying the MET cDNA; (iv) ligand-induced tyrosine phosphorylation of the Met beta subunit. SF and HGF cDNA clones from human fibroblasts, placenta and liver had virtually identical sequences. We conclude that the same molecule (SF/HGF) acts as a growth or motility factor through a single receptor in different target cells.
散射因子(SF)是一种由成纤维细胞分泌的蛋白质,可促进上皮细胞的运动和基质侵袭。肝细胞生长因子(HGF)是一种对肝细胞和其他上皮组织具有强大作用的促有丝分裂原。根据其各自的生物学活性纯化的SF和HGF在细胞生长、运动和侵袭检测中具有互换性且同样有效。二者以相同亲和力结合于靶细胞中的相同位点。通过以下方式确定SF和HGF的受体为MET癌基因的产物:(i)免疫复合物中的配体结合和共沉淀;(ii)与Metβ亚基的化学交联;(iii)携带MET cDNA的杆状病毒在昆虫细胞中转移结合活性;(iv)配体诱导的Metβ亚基酪氨酸磷酸化。来自人成纤维细胞、胎盘和肝脏的SF和HGF cDNA克隆具有几乎相同的序列。我们得出结论,同一分子(SF/HGF)通过不同靶细胞中的单一受体发挥生长或运动因子的作用。