Aoki S, Takahashi K, Matsumoto K, Nakamura T
Department of Oncology, Osaka University Medical School, Japan.
Biochem Biophys Res Commun. 1997 May 8;234(1):8-14. doi: 10.1006/bbrc.1997.6567.
Hepatocyte growth factor (HGF) specifically activates Met tyrosine kinase receptor, leading to mitogenic, motogenic, and morphogenic responses in a wide variety of cells. To know a role of HGF in Xenopus embryogenesis, loss-of-function mutation was introduced by dominant expression of truncated tyrosine kinase-negative Met. When tyrosine kinase-negative Met mRNA was micro-injected into two-cell to eight-cell stages Xenopus embryos, the liver development was mostly impaired and structures of pronephros and the gut were grossly underdeveloped in the restricted, late stage of development. These results strongly suggest that functional coupling between HGF and Met is essential for the development of internal organs originated from primitive gut and possibly involved in embryonic skeletogenesis. Together with developmental abnormality in mice mutated with HGF or Met gene, essential role of HGF for liver development is highly conserved from amphibian to mammalian species.
肝细胞生长因子(HGF)特异性激活Met酪氨酸激酶受体,从而在多种细胞中引发促有丝分裂、促运动和促形态发生反应。为了解HGF在非洲爪蟾胚胎发育中的作用,通过截短的酪氨酸激酶阴性Met的显性表达引入功能丧失突变。当将酪氨酸激酶阴性Met mRNA显微注射到两细胞至八细胞期的非洲爪蟾胚胎中时,肝脏发育大多受损,并且在发育的受限后期,前肾和肠道结构严重发育不全。这些结果强烈表明,HGF与Met之间的功能偶联对于源自原始肠道的内部器官的发育至关重要,并且可能参与胚胎骨骼形成。连同HGF或Met基因突变的小鼠中的发育异常一起,HGF对肝脏发育的重要作用在从两栖动物到哺乳动物物种中高度保守。