Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.
Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.
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发表时间：
1992
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影响因子：
8
通讯作者：
Ruth Halaban;Jeffrey S. Rubin;Yoko Funasaka;Melanie H. Cobb;Teri G. Boulton;D. Faletto;Eliot M. Rosen;Andrew Chan;Karen Yoko;W. White;Christopher Cook;Gisela Moellmann
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作者：
Ruth Halaban;Jeffrey S. Rubin;Yoko Funasaka;Melanie H. Cobb;Teri G. Boulton;D. Faletto;Eliot M. Rosen;Andrew Chan;Karen Yoko;W. White;Christopher Cook;Gisela Moellmann
原癌基因c-MET编码肝细胞生长因子/分散因子（HGF/SF）的跨膜酪氨酸激酶受体。HGF/SF刺激各种细胞类型的增殖和运动。由于HGF/SF也是黑素细胞有丝分裂原，我们研究了HGF/SF在正常和恶性人类黑素细胞中的生物学作用，包括c-Met表达、活化和信号转导。我们发现，HGF/SF是促有丝分裂的协同因素，如碱性成纤维细胞生长因子（bFGF）和肥大细胞生长因子（MGF）的存在下，本身，它刺激正常人黑素细胞的运动。配体还维持这些细胞中高水平的酪氨酸酶活性和黑色素含量。HGF/SF的信号转导包括c-Met上酪氨酰残基的磷酸化、其他几种蛋白质上酪氨酸磷酸化的级联反应以及微管相关蛋白激酶/细胞外信号调节激酶的激活。Met的表达和活性在人黑色素瘤中是正常的，并且HGF/SF在逆转录病毒感染的自主增殖的小鼠黑色素细胞中的组成性活性不足以赋予恶性表型。我们的研究结果表明，激活的Met响应HGF/SF可能有助于恶性进展协同异常表达的bFGF在恶性黑素细胞，此外，肽可能会促进分散的因素依赖性黑素细胞从早期阶段的原发性黑色素瘤异位网站。
The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites.