Yasunaga M, Yagi T, Hanzawa N, Yasuda M, Yamanashi Y, Yamamoto T, Aizawa S, Miyauchi Y, Nishikawa S
Department of Molecular Genetics, Faculty of Medicine, Kyoto University, Japan.
J Cell Biol. 1996 Jan;132(1-2):91-9. doi: 10.1083/jcb.132.1.91.
We analyzed the role of Fyn tyrosine kinase in cell cycle progression of B lymphocyte progenitor (pro B cell). Whereas there were no substantial defects in the intramarrow B cell genesis in the fyn(-) mouse, and long-term proliferation of fyn(-) pro B cells was maintained in vitro under a serum containing culture condition, the cell cycle was arrested at G2/M upon serum deprivation. Morphological analyses demonstrated that the cytokinesis of fyn(-) pro B cells was retarded in the presence of serum and that the entry of fyn(-) pro B cells into late telophase was completely blocked under the serum-free condition. In contrast, the earlier phases of mitosis of fyn(-) pro B cells proceeded normally without FCS. This failure to initiate late telophase resulted in the accumulation of elliptical binucleated cells that might be the outcome of the nuclear division without cytokinesis. Consistent with this defect in the progression of cytokinesis, Fyn was localized in the midspace of dividing pro B cells at anaphase. These results suggested that Fyn localizes at the midspace of dividing pro B cells and regulates the progression of cytokinesis.
我们分析了Fyn酪氨酸激酶在B淋巴细胞祖细胞(前B细胞)细胞周期进程中的作用。虽然fyn基因敲除小鼠的骨髓内B细胞生成没有明显缺陷,并且在含血清培养条件下,fyn基因敲除的前B细胞能够在体外维持长期增殖,但血清剥夺后细胞周期停滞在G2/M期。形态学分析表明,在有血清存在的情况下,fyn基因敲除的前B细胞的胞质分裂延迟,并且在无血清条件下,fyn基因敲除的前B细胞进入末期的过程被完全阻断。相比之下,在没有胎牛血清(FCS)的情况下,fyn基因敲除的前B细胞有丝分裂的早期阶段正常进行。无法启动末期导致椭圆形双核细胞的积累,这可能是没有胞质分裂的核分裂的结果。与胞质分裂进程中的这一缺陷一致,Fyn在分裂期的前B细胞中期定位于细胞中间区域。这些结果表明,Fyn定位于分裂期前B细胞的中间区域并调节胞质分裂进程。