A SINGLE AUTOPHOSPHORYLATION SITE CONFERS ONCOGENICITY TO THE NEU/ERBB-2 RECEPTOR AND ENABLES COUPLING TO THE MAP KINASE PATHWAY
A SINGLE AUTOPHOSPHORYLATION SITE CONFERS ONCOGENICITY TO THE NEU/ERBB-2 RECEPTOR AND ENABLES COUPLING TO THE MAP KINASE PATHWAY
复制标题
DOI：
10.1002/j.1460-2075.1994.tb06632.x
复制
发表时间：
1994-07-15
期刊：
影响因子：
11.4
通讯作者：
YARDEN, Y
中科院分区：
文献类型：
--
作者：
BENLEVY, R;PATERSON, HF;YARDEN, Y
Neu/ErbB-2受体酪氨酸激酶的转化潜力通过缺失非催化C-末端尾部（其含有5个自磷酸化位点）而失活。为了确定哪个位点是致癌性所必需的，我们用单个自磷酸化位点对C-末端缺失的突变体进行了跟踪。体外和体内转化作用的完全恢复由包含最C-末端酪氨酸自磷酸化位点（Y1253）的12个氨基酸的延伸赋予。重建的转化是特定于这个氨基酸序列，因为没有其他的自磷酸化位点，单独移植时，引起转化，并取代酪氨酸与苯丙氨酸残基显着降低了致癌潜力的全长和尾蛋白质。当单独存在时，最C-末端的序列能够耦合到一个生化途径，包括Ras，MAP激酶和转激活的六月。这些结果表明，受体酪氨酸激酶上的自磷酸化位点的多样性是不是必不可少的transformability，并牵连的MAP激酶途径在转导的致癌信号的Neu/ErbB-2。
The transforming potential of the Neu/ErbB-2 receptor tyrosine kinase undergoes inactivation by deletion of the non-catalytic C-terminal tail, which contains five autophosphorylation sites. To determine which site is essential for oncogenicity, we tailed the C-terminally-deleted mutant with individual autophosphorylation sites. Complete restoration of the transforming action in vitro and in vivo was conferred by a stretch of 12 amino acids that contained the most C-terminal tyrosine autophosphorylation site (Y1253). Reconstitution of transformation was specific to this amino acid sequence because none of the other autophosphorylation sites, when grafted individually, caused transformation, and replacement of the tyrosine with a phenylalanine residue significantly reduced the oncogenic potential of both the full-length and the tailed proteins. When present alone the most C-terminal sequence enabled coupling to a biochemical pathway that includes Ras, MAP kinase and transactivation of Jun. These results indicate that the multiplicity of autophosphorylation sites on a receptor tyrosine kinase is not essential for transformability, and implicate the MAP kinase pathway in transduction of the oncogenic signal of Neu/ErbB-2.