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首页> 外文期刊>Molecular and Cellular Biology >The Human c-Fes Tyrosine Kinase Binds Tubulin and Microtubules through Separate Domains and Promotes Microtubule Assembly
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The Human c-Fes Tyrosine Kinase Binds Tubulin and Microtubules through Separate Domains and Promotes Microtubule Assembly

机译：人类c-Fes酪氨酸激酶通过独立的域绑定微管蛋白和微管并促进微管组装。

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The c-Fes protein-tyrosine kinase (Fes) has been implicated in the differentiation of vascular endothelial, myeloid hematopoietic, and neuronal cells, promoting substantial morphological changes in these cell types. The mechanism by which Fes promotes morphological aspects of cellular differentiation is unknown. Using COS-7 cells as a model system, we observed that Fes strongly colocalizes with microtubules in vivo when activated via coiled-coil mutation or by coexpression with an active Src family kinase. In contrast, wild-type Fes showed a diffuse cytoplasmic localization in this system, which correlated with undetectable kinase activity. Coimmunoprecipitation and immunofluorescence microscopy showed that the N-terminal Fes/CIP4 homology (FCH) domain is involved in Fes interaction with soluble unpolymerized tubulin. However, the FCH domain was not required for colocalization with polymerized microtubules in vivo. In contrast, a functional SH2 domain was essential for microtubule localization of Fes, consistent with the strong tyrosine phosphorylation of purified tubulin by Fes in vitro. Using a microtubule nucleation assay, we observed that purified c-Fes also catalyzed extensive tubulin polymerization in vitro. Taken together, these results identify c-Fes as a regulator of the tubulin cytoskeleton that may contribute to Fes-induced morphological changes in myeloid hematopoietic and neuronal cells.
机译：c-Fes蛋白酪氨酸激酶（Fes）与血管内皮细胞，骨髓造血细胞和神经元细胞的分化有关，促进了这些细胞类型的实质性形态变化。 Fes促进细胞分化的形态方面的机制尚不清楚。使用COS-7细胞作为模型系统，我们观察到Fes通过盘绕线圈突变或与活性Src家族激酶共表达激活后，会与体内微管强烈共定位。相反，野生型Fes在该系统中显示出弥漫性胞质定位，这与不可检测的激酶活性相关。免疫共沉淀和免疫荧光显微镜检查显示N端Fes / CIP4同源性（FCH）域参与Fes与可溶性未聚合微管蛋白的相互作用。然而，在体内与聚合的微管共定位不需要FCH结构域。相反，功能性SH2结构域对Fes的微管定位至关重要，这与Fes在体外对纯化微管蛋白的强酪氨酸磷酸化作用相一致。使用微管成核试验，我们观察到纯化的c-Fes在体外也催化广泛的微管蛋白聚合。综上所述，这些结果确定了c-Fes是微管蛋白细胞骨架的调节剂，可能有助于Fes诱导的骨髓造血细胞和神经元细胞的形态变化。

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