非受体酪氨酸激酶c-Abl 通过磷酸化γ-Tubulin 调节细胞骨架

微管是主要的细胞骨架，在细胞形态维持、细胞有丝分裂等生命过程中具有重要作用。γ-Tubulin是微管起始聚合过程中微管成核的主要结构蛋白，对细胞微管形成具有重要作用。课题组前期发现γ-Tubulin 是非受体酪氨酸激酶c-Abl的底物，c-Abl可以通过磷酸化γ-Tubulin，调节细胞内微管的合成和细胞有丝分裂。本项目将详细研究c-Abl 激酶与γ-Tubulin 的相互作用及磷酸化，深入研究c-Abl通过γ-Tubulin 调控细胞骨架形成、有丝分裂中纺锤体和分裂沟形成的分子机制，同时探索c-Abl抑制剂和其它微管靶向药物联合用于c-Abl高活性肿瘤的可能性。

Microtubules are the major eukaryotic cytoskeleton components which play vital roles in the maintenance of cell shape, mitosis and other cellular activities. γ-Tubulin, mainly localized in microtubule-organizing center, can be organized into microtubule nucleator complex, which initiates the biogenesis of microtubule. Our primary results demonstrated that γ-Tubulin could associate with and be phosphorylated by non-receptor tyrosine kinases c-Abl and Arg, which regulates microtubules synthesis and mitosis. In this study, We will delineate the mechanism of c-Abl/Arg and γ-Tubulin interaction in the regulation of cytoskeleton, spindle and cleavage furrow formation in mitosis, hence provide insight in the combined application of c-Abl specific inhibitors and other microtubules-targeted drugs in tumor treatment.