TYROSINE KINASE-ACTIVITY AND TRANSFORMATION POTENCY OF BCR-ABL ONCOGENE PRODUCTS

TYROSINE KINASE-ACTIVITY AND TRANSFORMATION POTENCY OF BCR-ABL ONCOGENE PRODUCTS
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DOI:
10.1126/science.2408149
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发表时间:
1990-03-02
期刊:
影响因子:
56.9
通讯作者:
WITTE, ON
WITTE, ON
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LUGO, TG;PENDERGAST, AM;WITTE, ON

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在人类白血病中,原癌基因c-abl的致癌激活是由于bcr基因外显子的添加和第一个abl外显子的截断。酪氨酸激酶活性分析和单步法转化效能的定量测量表明,bcr外显子贡献的差异导致p210bcr-abl和p185bcr-abl蛋白的功能差异。因此,外源上游序列在abl产物激酶活性的调节中是重要的,调节的程度与bcr-abl蛋白的病理作用相关。
Oncogenic activation of the proto-oncogene c-abl in human leukemias occurs as a result of the addition of exons from the gene bcr and truncation of the first abl exon. Analysis of tyrosine kinase activity and quantitative measurement of transformation potency in a single-step assay indicate that variation in bcr exon contribution results in a functional difference between p210bcr-abl and p185bcr-abl proteins. Thus, foreign upstream sequences are important in the deregulation of the kinase activity of the abl product, and the extent of deregulation correlates with the pathological effects of the bcr-abl proteins.