Specific protein phosphorylation in human promyelocytic HL-60 leukemia cells susceptible or resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate.
Specific protein phosphorylation in human promyelocytic HL-60 leukemia cells susceptible or resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate.
复制标题
对 phorbol-12-myristate-13-acetate 诱导细胞分化敏感或抵抗的人早幼粒细胞 HL-60 白血病细胞中的特异性蛋白磷酸化。
作者：
N. Anderson;M. Gemmell;P. Coussens;S. Murao;E. Huberman
在人HL-60白血病细胞和HL-60细胞变体R-94细胞中，通过二维凝胶电泳分析了佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）诱导的蛋白磷酸化模式，其中人HL-60白血病细胞对PMA诱导的细胞分化敏感，而HL-60细胞变体R-94对这种诱导具有抗性。通过观察[35 S]甲硫氨酸标记的蛋白质的快速酸导向电荷转移或32 P标记的蛋白质中磷酸盐标记量的增加来检测蛋白质磷酸化。结果表明，PMA在10（-7）M处理后30分钟内，HL-60和R-94细胞中至少有10种不同蛋白质磷酸化。在这10个磷酸化的蛋白质，我们确定了一个主要的细胞质多肽（先生约64,000），细胞骨架蛋白（先生约56,000），非肌肉肌球蛋白轻链，和两个蛋白质（先生约60,000和64,000）定位在细胞核内或周围。10种磷蛋白中有6种的磷酸氨基酸分析表明它们含有磷酸丝氨酸。这些蛋白质均不含磷酸酪氨酸或磷酸苏氨酸。发现R-94细胞变体在PMA处理后能够增加蛋白磷酸化;然而，磷酸盐掺入水平仅达到未处理的HL-60细胞的水平，因此远远低于PMA处理后在HL-60细胞中观察到的水平。这表明，R-94细胞对PMA诱导细胞分化的获得性抗性的基础是在诱导剂PMA与其受体（蛋白激酶C）结合后，涉及核蛋白磷酸化的信号传递受阻。
The pattern of protein phosphorylation induced by phorbol-12-myristate-13-acetate (PMA) was analyzed by two-dimensional gel electrophoresis in human HL-60 leukemia cells, which are susceptible to induction of cell differentiation by PMA, and in cells from an HL-60 cell variant designated R-94 that are resistant to such an induction. Protein phosphorylation was detected by observing either a rapid acid-directed charge shift of [35S]methionine-labeled protein or an increase in the amount of phosphate label in a 32P-labeled protein. The results indicated that PMA at 10(-7) M causes within 30 min after treatment the phosphorylation of at least ten different proteins in both the HL-60 and R-94 cells. Among these ten phosphorylated proteins, we identified a major cytoplasmic polypeptide (Mr approximately 64,000), a cytoskeletal protein (Mr approximately 56,000), a nonmuscle myosin light chain, and two proteins (Mr approximately 60,000 and 64,000) localized in or around the cell nucleus. Phosphoamino acid analysis of six of the ten phosphoproteins showed that they contain phosphoserine. None of these proteins contained phosphotyrosine or phosphothreonine. The R-94 cell variant was found to be capable of increased protein phosphorylation after PMA treatment; however, the level of phosphate incorporation reached only the level of the untreated HL-60 cells and thus fell far short of the level observed in the HL-60 cells after PMA treatment. It is suggested that the basis for the acquired resistance in R-94 cells towards induction of cell differentiation by PMA is a block in signal transmission involving phosphorylation of nuclear protein(s) following the binding of the inducer PMA to its receptor (protein kinase C).
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影响因子：
11.2
作者：
H. Koeffler;M. Bar‐eli;M. Territo
通讯作者：
H. Koeffler;M. Bar‐eli;M. Territo
佛波二酯在分化人骨髓 HL-60 白血病细胞中对磷脂甲基化的控制。
影响因子：
4.7
作者：
Hoffman,DR;Huberman,E
通讯作者：
Huberman,E
对 12-O-十四烷酰佛波醇-13-乙酸酯诱导分化敏感和耐药的人早幼粒细胞白血病细胞的膜脂质动力学。
影响因子：
11.2
作者：
Fisher,PB;Schachter,D;Abbott,RE;Callaham,MF;Huberman,E
通讯作者：
Huberman,E
DOI：
10.1073/pnas.80.1.36
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
NIEDEL, JE;KUHN, LJ;VANDENBARK, GR
通讯作者：
VANDENBARK, GR
佛波酯诱导白血病细胞分化是一个膜介导的过程。
DOI：
10.1073/pnas.79.9.2865
发表时间：
1982
影响因子：
11.1
作者：
Cooper,RA;Braunwald,AD;Kuo,AL
通讯作者：
Kuo,AL