Shuster C B, Burgess D R
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Cell Biol. 1999 Sep 6;146(5):981-92. doi: 10.1083/jcb.146.5.981.
One model for the timing of cytokinesis is based on findings that p34(cdc2) can phosphorylate myosin regulatory light chain (LC20) on inhibitory sites (serines 1 and 2) in vitro (Satterwhite, L.L., M.H. Lohka, K.L. Wilson, T.Y. Scherson, L.J. Cisek, J.L. Corden, and T.D. Pollard. 1992. J. Cell Biol. 118:595-605), and this inhibition is proposed to delay cytokinesis until p34(cdc2) activity falls at anaphase. We have characterized previously several kinase activities associated with the isolated cortical cytoskeleton of dividing sea urchin embryos (Walker, G.R., C.B. Shuster, and D.R. Burgess. 1997. J. Cell Sci. 110:1373-1386). Among these kinases and substrates is p34(cdc2) and LC20. In comparison with whole cell activity, cortical H1 kinase activity is delayed, with maximum levels in cortices prepared from late anaphase/telophase embryos. To determine whether cortical-associated p34(cdc2) influences cortical myosin II activity during cytokinesis, we labeled eggs in vivo with [(32)P]orthophosphate, prepared cortices, and mapped LC20 phosphorylation through the first cell division. We found no evidence of serine 1,2 phosphorylation at any time during mitosis on LC20 from cortically associated myosin. Instead, we observed a sharp rise in serine 19 phosphorylation during anaphase and telophase, consistent with an activating phosphorylation by myosin light chain kinase. However, serine 1,2 phosphorylation was detected on light chains from detergent-soluble myosin II. Furthermore, cells arrested in mitosis by microinjection of nondegradable cyclin B could be induced to form cleavage furrows if the spindle poles were physically placed in close proximity to the cortex. These results suggest that factors independent of myosin II inactivation, such as the delivery of the cleavage stimulus to the cortex, determine the timing of cytokinesis.
在体外,p34(cdc2)能够使肌球蛋白调节轻链(LC20)的抑制位点(丝氨酸1和2)发生磷酸化(萨特怀特,L.L.,M.H.洛卡,K.L.威尔逊,T.Y.舍尔森,L.J.西塞克,J.L.科登,以及T.D.波拉德。1992年。《细胞生物学杂志》118:595 - 605),并且这种抑制作用被认为会延迟胞质分裂,直到p34(cdc2)的活性在后期下降。我们之前已经对分离的正在分裂的海胆胚胎皮质细胞骨架相关的几种激酶活性进行了表征(沃克,G.R.,C.B.舒斯特,以及D.R.伯吉斯。1997年。《细胞科学杂志》110:1373 - 1386)。在这些激酶和底物中包括p34(cdc2)和LC20。与全细胞活性相比,皮质H1激酶活性出现延迟,在由后期/末期胚胎制备的皮质中达到最高水平。为了确定在胞质分裂过程中与皮质相关的p34(cdc2)是否会影响皮质肌球蛋白II的活性,我们在体内用[³²P]正磷酸盐标记卵子,制备皮质,并通过第一次细胞分裂绘制LC20磷酸化图谱。我们没有发现有丝分裂期间任何时候皮质相关肌球蛋白的LC20上存在丝氨酸1、2磷酸化的证据。相反,我们观察到后期和末期丝氨酸19磷酸化急剧增加,这与肌球蛋白轻链激酶的激活磷酸化一致。然而,在去污剂可溶的肌球蛋白II轻链上检测到了丝氨酸1、2磷酸化。此外,如果将纺锤极物理性地靠近皮质放置,通过显微注射不可降解的细胞周期蛋白B使细胞停滞在有丝分裂期时可以诱导形成分裂沟。这些结果表明,与肌球蛋白II失活无关的因素,如将分裂刺激传递到皮质,决定了胞质分裂的时间。