Besser D, Bromberg J F, Darnell J E, Hanafusa H
Laboratory of Molecular Oncology, The Rockefeller University, New York, New York 10021, USA.
Mol Cell Biol. 1999 Feb;19(2):1401-9. doi: 10.1128/MCB.19.2.1401.
The receptor tyrosine kinase Eyk, a member of the Axl/Tyro3 subfamily, activates the STAT pathway and transforms cells when constitutively activated. Here, we compared the potentials of the intracellular domains of Eyk molecules derived from c-Eyk and v-Eyk to transform rat 3Y1 fibroblasts. The v-Eyk molecule induced higher numbers of transformants in soft agar and stronger activation of Stat3; levels of Stat1 activation by the two Eyk molecules were similar. A mutation in the sequence Y933VPL, present in c-Eyk, to the v-Eyk sequence Y933VPQ led to increased activation of Stat3 and increased transformation efficiency. However, altering another sequence, Y862VNT, present in both Eyk molecules to F862VNT markedly decreased transformation without impairing Stat3 activation. These results indicate that activation of Stat3 enhances transformation efficiency and cooperates with another pathway to induce transformation.
受体酪氨酸激酶Eyk是Axl/Tyro3亚家族的成员之一，在组成性激活时可激活STAT信号通路并使细胞发生转化。在此，我们比较了源自c-Eyk和v-Eyk的Eyk分子胞内结构域转化大鼠3Y1成纤维细胞的能力。v-Eyk分子在软琼脂中诱导产生的转化子数量更多，对Stat3的激活更强；两种Eyk分子对Stat1的激活水平相似。c-Eyk中存在的序列Y933VPL突变为v-Eyk序列Y933VPQ会导致Stat3激活增加和转化效率提高。然而，将两种Eyk分子中都存在的另一个序列Y862VNT改变为F862VNT，在不损害Stat3激活的情况下显著降低了转化效率。这些结果表明，Stat3的激活增强了转化效率，并与另一条信号通路协同诱导细胞转化。
