The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules.
The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules.
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DOI：
10.1016/j.yexcr.2005.02.014
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发表时间：
2005-05
影响因子：
3.7
通讯作者：
Anjali M Teckchandani;A. Birukova;K. Tar;A. Verin;A. Tsygankov
中科院分区：
文献类型：
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作者：
Anjali M Teckchandani;A. Birukova;K. Tar;A. Verin;A. Tsygankov
已知原癌蛋白c-Cbl调节肌动蛋白细胞骨架。在这项研究中，我们提出的结果表明，c-Cbl也可以调节微管网络。我们已经证明，c-Cbl通过其酪氨酸激酶结合(TKB)结构域与微管蛋白和微管结合。然而，本报告中描述的相互作用的特征是新的，因为G306E突变破坏了c-Cbl的TKB与酪氨酸磷酸化蛋白结合的能力，并不影响观察到的c-Cbl与微管之间的相互作用。此外，c-Cbl在人肺动脉内皮细胞和COS-7细胞中的过表达导致微管稳定。我们证明，c-Cbl的这种作用是由TKB介导的，并且，就像c-Cbl与微管的结合一样，它与TKB与酪氨酸磷酸化蛋白的结合能力无关。最后，我们证明了c-Cbl在体外直接聚合微管，而TKB是c-Cb1这一作用的必要条件和充分条件。在最后一种现象中，与之前的现象一样，TKB的作用对失活的G306E突变不敏感。总体而言，本报告提出了一种新的c-Cbl-微管结合和稳定功能。
The protooncogenic protein c-Cbl is known to regulate the actin cytoskeleton. In this study, we present results indicating that c-Cbl can also regulate the microtubular network. We have shown that c-Cbl binds to tubulin and microtubules through its tyrosine kinase binding (TKB) domain. However, the character of the interactions described in this report is novel, since the G306E mutation, which disrupts the ability of c-Cbl's TKB to bind to tyrosine-phosphorylated proteins, does not affect the observed interaction between c-Cbl and microtubules. Furthermore, overexpression of c-Cbl in human pulmonary artery endothelial cells and COS-7 cells leads to microtubule stabilization. We demonstrate that this effect of c-Cbl is mediated by TKB, and, like c-Cbl binding to microtubules, is independent of the ability of TKB to bind to tyrosine-phosphorylated proteins. Finally, we have shown that c-Cbl directly polymerizes microtubules in vitro, and that TKB is necessary and sufficient for this effect of c-Cbl. In this last phenomenon, as well as in the previous ones, the effect of TKB is not sensitive to the inactivating G306E mutation. Overall, the results presented in this report suggest a novel function for c-Cbl—microtubule binding and stabilization.