TYROSINE KINASE RECEPTOR INDISTINGUISHABLE FROM THE C-MET PROTEIN
TYROSINE KINASE RECEPTOR INDISTINGUISHABLE FROM THE C-MET PROTEIN
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DOI：
10.1038/339155a0
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发表时间：
1989-05-11
期刊：
影响因子：
64.8
通讯作者：
COMOGLIO, PM
中科院分区：
文献类型：
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作者：
GIORDANO, S;PONZETTO, C;COMOGLIO, PM
具有蛋白酪氨酸激酶活性的生长因子受体对控制正常和恶性细胞的增殖至关重要1 -3。使用抗磷酸酪氨酸抗体4，我们以前已经确定了一个跨膜糖蛋白与异常高的蛋白酪氨酸激酶活性在人胃癌细胞系（GTL-16）5，6。非还原条件下的电泳显示，该激酶（相对分子质量145，000（145 K））以二硫键连接至190 K（p190）αβ复合物中的50 K链。从其新颖的双链结构，我们推断p190是一类新的酪氨酸激酶受体的原型。我们现在发现，p190与c-原癌基因编码的蛋白质是不可区分的，并且αβ亚基结构在其他人类细胞系中是保守的。我们还表明，在GTL-16细胞系中发现的高水平的p190伴随着扩增和c-met的过表达。这提供了c-metin在人肿瘤细胞系中功能改变的第一个例子。
GROWTH factor receptors with protein tyrosine kinase activity are central to the control of proliferation of both normal and malignant cells1–3. Using anti-phosphotyrosine antibodies4, we have previously identified a transmembrane glycoprotein with abnormally high protein tyrosine kinase activity in a human gastric tumour cell line (GTL-16)5,6. Electrophoresis under non-reducing conditions revealed that this kinase (relative molecular mass 145,000 (145 K)) is disulphide-linked to a 50K chain in an αβ-complex of 190K (p190). From its novel two-chain structure, we deduced that p190 was the prototype of a new class of tyrosine kinase receptors. We now show that p190 is indistinguishable from the protein encoded by the c-metprotooncogene and that the αβ-subunit structure is conserved in other human cell lines. We also show that the high level of p190 found in the GTL-16 cell line is accompanied by amplification and overexpression of c-met. This provides the first example of a functional alteration of c-metin a human tumour cell line.