Franz W M, Berger P, Wang J Y
Department of Biology, UCSD, La Jolla 92093.
EMBO J. 1989 Jan;8(1):137-47. doi: 10.1002/j.1460-2075.1989.tb03358.x.
The requirements for the oncogenic conversion of the c-abl proto-oncogene have been determined by the expression of N-terminal deleted forms and viral gag-fused forms of the c-abl proteins from a selectable retroviral vector. To activate the transforming potential of c-abl, it is necessary that (i) specific N-terminal amino acids are deleted to release the kinase from negative regulation in vivo; (ii) an N-terminal myristylation site is part of the activated kinase; (iii) the fatty-acylated, activated kinase is overproduced. The N-terminal amino acids found to be necessary for the cellular inhibition of c-abl tyrosine phosphorylation are part of a homologous region present in many non-receptor tyrosine kinases, the v-crk oncogene and phospholipase C-II. Overproduction of a deregulated and myristylated c-abl tyrosine kinase induces the transformation of NIH 3T3 cells.
通过从可选择的逆转录病毒载体表达c-abl蛋白的N端缺失形式和病毒gag融合形式，已确定了c-abl原癌基因致癌转化的要求。为激活c-abl的转化潜能，有必要：（i）删除特定的N端氨基酸以在体内使激酶从负调控中释放出来；（ii）N端肉豆蔻酰化位点是活化激酶的一部分；（iii）过量产生脂肪酰化的活化激酶。发现对c-abl酪氨酸磷酸化进行细胞抑制所必需的N端氨基酸是许多非受体酪氨酸激酶、v-crk癌基因和磷脂酶C-II中存在的同源区域的一部分。失调且肉豆蔻酰化的c-abl酪氨酸激酶的过量产生诱导NIH 3T3细胞的转化。
