Jackowski S
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
J Biol Chem. 1994 Feb 4;269(5):3858-67.
The formation of membrane phospholipid is coordinated with the cell cycle in a colony-stimulating factor 1-dependent macrophage cell line. Net phospholipid accumulation occurs as cells enter S phase and results from an interaction between cell cycle-dependent oscillations in the rates of phosphatidylcholine (PtdCho) biosynthesis and degradation. CTP:phosphocholine cytidylyltransferase (CT) is the rate-controlling step in PtdCho biosynthesis, and its activity is inhibited by cell cycle-dependent phosphorylation. CT phosphorylation is low in early G1, begins to rise in late G1, increases steadily through S and G2/M, and then declines precipitously as cells exit mitosis and reenter G1. CT activity increases in early G1 and then decreases steadily as the cells progress through late G1, S, and G2/M, reflecting the elevated phosphorylation state of the protein. Membrane phospholipid degradation is also periodic: the rate is rapid in G1, slows significantly during S phase, and accelerates again as cells reenter G1. The data support the hypothesis that CT dephosphorylation accelerates PtdCho synthesis in response to the increased membrane phospholipid degradation to maintain membrane phospholipid mass during G1 and that the periodic cessation of phospholipid degradation during S phase accounts for the transition to net membrane phospholipid accumulation. Inactivation of CT associated with hyperphosphorylation of the protein during G2/M likely plays a determining role in the cessation of net membrane accumulation prior to cell division.
在集落刺激因子1依赖的巨噬细胞系中，膜磷脂的形成与细胞周期相协调。当细胞进入S期时会发生净磷脂积累，这是由磷脂酰胆碱（PtdCho）生物合成和降解速率的细胞周期依赖性振荡之间的相互作用导致的。CTP：磷酸胆碱胞苷转移酶（CT）是PtdCho生物合成中的限速步骤，其活性受到细胞周期依赖性磷酸化的抑制。CT磷酸化在G1早期较低，在G1晚期开始上升，在S期和G2/M期稳步增加，然后随着细胞退出有丝分裂并重新进入G1期而急剧下降。CT活性在G1早期增加，然后随着细胞经过G1晚期、S期和G2/M期而稳步下降，这反映了该蛋白的磷酸化状态升高。膜磷脂降解也是周期性的：在G1期速率很快，在S期显著减慢，并且随着细胞重新进入G1期再次加速。这些数据支持以下假设：CT去磷酸化响应于膜磷脂降解增加而加速PtdCho合成，以在G1期维持膜磷脂总量，并且S期磷脂降解的周期性停止解释了向净膜磷脂积累的转变。在G2/M期与该蛋白过度磷酸化相关的CT失活可能在细胞分裂前净膜积累停止中起决定性作用。
