Mechanism of activation of the human trk oncogene.
Mechanism of activation of the human trk oncogene.
复制标题
人类trk癌基因的激活机制。
DOI：
10.1128/mcb.9.1.15-23.1989
复制
发表时间：
1989
影响因子：
5.3
通讯作者：
Barbacid,M
中科院分区：
文献类型：
--
作者：
Coulier,F;Martin-Zanca,D;Ernst,M;Barbacid,M
The humantrkoncogene was generated by a genetic rearrangement that replaced the extracellular domain of the normaltrktyrosine kinase receptor by sequences coding for the 221 amino-terminal residues of a nonmuscle tropomyosin. Molecular dissection of a cDNA clone of thetrkoncogene indicated that both the tropomyosin and tyrosine kinase domains were required for proper transforming activity. Replacement of nonmuscle tropomyosin sequences with those of other tropomyosin isoforms had no deleterious effect. However, when tropomyosin sequences were replaced with those of another cytoskeletal gene, such as β-actin or β-globin, transforming activity was completely abolished. These results illustrate the important role of tropomyosin sequences in endowing thetrkkinase with transforming properties. Functionally unrelated subdomains of the tropomyosin molecule were equally efficient in activating thetrkgene. Moreover, the transforming activity of thetrkoncogene was not affected when its subcellular localization was drastically altered. Therefore, tropomyosin sequences are likely to contribute to the malignant activation of thetrkoncogene not by facilitating its interaction with defined cytoskeletal structures as initially suspected, but by allowing its kinase domain to fold into a constitutively active configuration.
