Requirement of the coiled-coil domains of p92c-Fes for nuclear localization in myeloid cells upon induction of differentiation
Requirement of the coiled-coil domains of p92c-Fes for nuclear localization in myeloid cells upon induction of differentiation
复制标题
诱导分化时骨髓细胞核定位需要 p92c-Fes 的卷曲螺旋结构域
作者：
E. Tagliafico;M. Siena;T. Zanocco;R. Manfredini;E. Tenedini;M. Montanari;A. Grande;S. Ferrari
非受体酪氨酸激酶Fes与髓细胞分化有关。已观察到其定位可以是细胞质，核周或核。为了进一步表征这一点，我们研究了Fes在髓系（HL60和K562）和COS1细胞中的亚细胞定位。过表达Fes的HL60、K562细胞的细胞核和细胞质中均可见Fes，而仅在COS1细胞的细胞质中可见Fes，表明核定位与细胞环境有关。此外，在髓细胞中，用维甲酸、佛酚酯和维生素D等分化诱导剂处理后，细胞核中Fes的低聚形式增加。事实上，低聚化似乎是易位发生的必要条件，因为缺少螺旋结构域的Fes突变体不能形成低聚体，也不能在细胞核中定位。Fes的活性形式是酪氨酸磷酸化；然而，Fes在细胞核中定位不需要磷酸化，因为酪氨酸激酶抑制剂不会阻断易位过程。
The nonreceptor tyrosine kinase Fes is implicated in myeloid cells differentiation. It has been observed that its localization can be cytoplasmic, perinuclear, or nuclear. To further characterize this point, we studied Fes subcellular localization in myeloid cell lines (HL60 and K562) and in COS1 cells. Fes was observed in both the nucleus and the cytoplasm of HL60, K562 cells overexpressing Fes and only in the cytoplasm of COS1 cells, suggesting that nuclear localization is cell context dependent. Moreover, in myeloid cells, the treatment with differentiation-inducing agents such as retinoic acid, phorbol esters and vitamin D, is followed by an increase of the oligomeric form of Fes in the nucleus. In fact, oligomerization seems to be necessary for translocation to occur, since Fes mutants missing the coiled-coil domains are not able to form oligomers and fail to localize in the nucleus. The active form of Fes is tyrosine phosphorylated; however, phosphorylation is not required for Fes to localize in the nucleus, since tyrosine kinase inhibitors do not block the translocation process.