Evidence for non-covalent clusters of the c-met proto-oncogene product.
Evidence for non-covalent clusters of the c-met proto-oncogene product.
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发表时间：
1992-06
期刊：
影响因子：
8
通讯作者：
D. Faletto;I. Tsarfaty;T. Kmiecik;M. Gonzatti;T. Suzuki;G. V. Vande Woude
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文献类型：
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作者：
D. Faletto;I. Tsarfaty;T. Kmiecik;M. Gonzatti;T. Suzuki;G. V. Vande Woude
met原癌基因是酪氨酸激酶生长因子受体家族的成员，并且是肝细胞生长因子（HGF）或分散因子的受体。主要met产物是150 kDa前体，其被糖基化以产生170 kDa（p170 met）前受体蛋白。受体的成熟形式通过裂解p170 met产生二硫键连接的140 kDa β亚基（p140 met）和45 kDa α亚基（p45 met）。两种产物都是糖基化的。在非还原条件下，p170 met和α，β-二硫键连接的蛋白质均被检测为185 kDa产物（p185 met），但只有α-β异二聚体p185 met被交联，并对膜不可渗透的6.4 A接头长度交联试剂的二硫键还原具有抗性。这些数据表明p170前体不在细胞表面。使用12-A接头试剂的交联实验产生大小大于500 kDa的α-β异二聚体p185 met的多聚体形式。这些多聚体形式在所有测试的细胞系中产生，而不管表达的蛋白质水平如何。这些数据表明，α-β异源二聚体p185 met发生在细胞表面的集群或补丁。在配体的情况下，met蛋白的免疫组织化学分析揭示了细胞表面的成簇染色模式。
The met proto-oncogene is a member of the tyrosine kinase growth factor receptor family and is the receptor for hepatocyte growth factor (HGF) or scatter factor. The primary met product is a 150 kDa precursor that is glycosylated to generate a 170 kDa (p170met) proreceptor protein. The mature form of the receptor is generated by cleavage of p170met to yield a disulfide-linked 140 kDa beta-subunit (p140met) and a 45 kDa alpha-subunit (p45met). Both products are glycosylated. Under non-reducing conditions both p170met and the alpha, beta-disulfide-linked protein are detected as a 185 kDa product (p185met), but only alpha-beta heterodimeric p185met is cross-linked and rendered resistant to disulfide reduction with membrane-impermeable 6.4 A linker length cross-linking reagents. These data indicate that the p170 precursor is not on the cell surface. Cross-linking experiments using 12-A linker reagents yield multimeric forms of alpha-beta heterodimeric p185met greater than 500 kDa in size. These multimeric forms are produced in all cell lines tested regardless of the levels of protein expressed. These data suggest that alpha-beta heterodimeric p185met occurs in clusters or patches on the cell surface. Immunohistochemical analysis of met protein in the absence of ligand reveals a clustered staining pattern on the cell surface.