DIFFERENTIAL COMPLEMENTATION OF BCR-ABL POINT MUTANTS WITH C-MYC
DIFFERENTIAL COMPLEMENTATION OF BCR-ABL POINT MUTANTS WITH C-MYC
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DOI：
10.1126/science.8153630
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发表时间：
1994-04-15
期刊：
影响因子：
56.9
通讯作者：
SAWYERS, CL
中科院分区：
文献类型：
--
作者：
AFAR, DEH;GOGA, A;SAWYERS, CL
开发了互补策略来定义由Bcr-Abl酪氨酸激酶激活的信号通路。测试Bcr-Abl的转化失活点突变体与c-Myc的互补。Src同源性2（SH 2）结构域（激酶结构域的主要酪氨酸自磷酸化位点）和Bcr区域中Grb-2结合位点的单点突变损害了Bcr-Abl对成纤维细胞的转化。这些数据支持Bcr-Abl激活至少两个独立的转化途径的模型。这种策略可能有助于识别由其他癌基因激活的信号通路。
A complementation strategy was developed to define the signaling pathways activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of the kinase domain, and the Grb-2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently restored transformation activity only to the Bcr-Abl SH2 mutant. These data support a model in which Bcr-Abl activates at least two independent pathways for transformation. This strategy may be useful for discerning signaling pathways activated by other oncogenes.