Anti-oncogenic activity of signalling-defective epidermal growth factor receptor mutants
Anti-oncogenic activity of signalling-defective epidermal growth factor receptor mutants
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信号传导缺陷型表皮生长因子受体突变体的抗癌活性
DOI：
--
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发表时间：
1992
影响因子：
5.3
通讯作者：
A. Ullrich
中科院分区：
文献类型：
--
作者：
N. Redemann;'. B. Holzmann;T. V. Ruden;E. Wagner;J. Schlessinger;A. Ullrich
表皮生长因子受体（EGF-R）的过表达和自分泌激活导致培养细胞的转化，并与癌症患者的肿瘤进展相关。二聚化和转磷酸化是具有酪氨酸激酶活性的受体产生正常和转化细胞信号的过程中的关键事件。通过非活性受体突变体中断该过程提供了抑制配体诱导的细胞反应的潜力。使用重组逆转录病毒，我们已经研究了信号无能的EGF-R突变体的配体激活，过度表达的野生型EGF-R和v-erbB癌基因产物的生长促进和转化潜力的影响。可溶性细胞外EGF-R结构域的表达对NIH 3 T3细胞的生长和转化几乎没有任何影响。然而，激酶阴性的EGF-R点突变体（HERK 721 A）和缺乏533个C-末端氨基酸的EGF-R均以剂量依赖性方式有效抑制野生型EGF-R介导的从头DNA合成和细胞转化。此外，在NIH 3 T3细胞中与v-erbBES 4癌基因产物共表达导致HERK 721 A突变受体的转磷酸化，并减少软琼脂集落生长，但在病灶形成试验中没有影响。这些结果表明，信号缺陷型受体酪氨酸激酶突变体差异干扰致癌信号产生的过度表达的EGF-R或逆转录病毒v-erbBES 4癌基因产物。
Overexpression and autocrine activation of the epidermal growth factor receptor (EGF-R) cause transformation of cultured cells and correlate with tumor progression in cancer patients. Dimerization and transphosphorylation are crucial events in the process by which receptors with tyrosine kinase activity generate normal and transforming cellular signals. Interruption of this process by inactive receptor mutants offers the potential to inhibit ligand-induced cellular responses. Using recombinant retroviruses, we have examined the effects of signalling-incompetent EGF-R mutants on the growth-promoting and transforming potential of ligand-activated, overexpressed wild-type EGF-R and the v-erbB oncogene product. Expression of a soluble extracellular EGF-R domain had little if any effect on the growth and transformation of NIH 3T3 cells by either tyrosine kinase. However, both a kinase-negative EGF-R point mutant (HERK721A) and an EGF-R lacking 533 C-terminal amino acids efficiently inhibited wild-type EGF-R-mediated, de novo DNA synthesis and cell transformation in a dose-dependent manner. Furthermore, coexpression with the v-erbBES4 oncogene product in NIH 3T3 cells resulted in transphosphorylation of the HERK721A mutant receptor and reduced soft-agar colony growth but had no effect in a focus formation assay. These results demonstrate that signalling-defective receptor tyrosine kinase mutants differentially interfere with oncogenic signals generated by either overexpressed EGF-R or the retroviral v-erbBES4 oncogene product.
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TGF α整合膜前体的表达诱导NRK细胞的转化。
影响因子：
8
作者：
Blasband,AJ;Gilligan,DM;Winchell,LF;Wong,ST;Luetteke,NC;Rogers,KT;Lee,DC
通讯作者：
Lee,DC
影响因子：
10.5
作者：
NOCKA, K;MAJUMDER, S;BESMER, P
通讯作者：
BESMER, P
DOI：
10.1016/s0021-9258(19)75716-0
发表时间：
1987-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Chou;T. Dull;D. Russell;R. Gherzi;D. Lebwohl;A. Ullrich;O. Rosen
通讯作者：
C. Chou;T. Dull;D. Russell;R. Gherzi;D. Lebwohl;A. Ullrich;O. Rosen
DOI：
10.1016/s0021-9258(18)69070-2
发表时间：
1988-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Cochet;O. Kashles;E. Chambaz;I. Borrello;C. King;J. Schlessinger
通讯作者：
C. Cochet;O. Kashles;E. Chambaz;I. Borrello;C. King;J. Schlessinger
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL