| Autor: |
Ikebuchi, Fumie, Oka, Kiyomasa, Mizuno, Shinya, Fukuta, Kazuhiro, Hayata, Daichika, Ohnishi, Hiroyuki, Nakamura, Toshikazu |
| Zdroj: |
Cell Biochemistry & Function; Jun2013, Vol. 31 Issue 4, p298-304, 7p |
| Abstrakt: |
Hepatocyte growth factor (HGF) is essential for embryogenesis, tissue regeneration and tumour malignancy through the activation of its receptor, c-Met. We previously demonstrated that HGF α-chain hairpin-loop, K1 domain and β-chain are required for c-Met signalling. The sequential phosphorylation of tyrosine residues, from c-Met kinase domain to multidocking regions, is required for HGF-signalling transduction. Herein, we provide evidence that the disconcerted activation of c-Met tyrosine regions fails to induce biological functions. When human cells were incubated with 'mouse HGF', kinase domain activation (i.e. phospho-Tyr-1230/34/35) became evident, but the multidocking site ( i.e. Tyr-1349) was not phosphorylated, resulting in unsuccessful induction of migration and mitogenesis. The binding ability of mouse HGF α-chain, or of β-chain, to human c-Met was lower than that of human HGF, as evidenced by HGF-chimera assay. Notably, only four amino acid positions in HGF α-chain hairpin-loop and K1 domain and six positions in β-chain differed between human HGF and mouse HGF. The human-specific amino acids (such as Gln-95 in hairpin-loop, Arg-134 in K1 domain and Cys-561 in β-chain) may be important for accurate c-Met assembly and signalling transduction. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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