Protein kinase C (cid:1) mediates retinoic acid and phorbol myristate acetate–induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation
Protein kinase C (cid:1) mediates retinoic acid and phorbol myristate acetate–induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation
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磷脂攀爬酶1（PLSCR1）基于其促进膜磷脂的跨双层运动的能力，随后的研究也提供了其在细胞增殖、成熟和凋亡中的作用的证据。在这份报告中，我们调查PLSCR1在白血病细胞分化的潜在作用。我们发现，全反式维甲酸（ATRA），一种有效的急性早幼粒细胞白血病（APL）细胞分化诱导剂，可以提高PLSCR1在ATRA敏感的APL细胞NB4和HL 60中的表达，但不能在成熟抵抗的NB4-LR 1细胞中表达。ATRA和佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的单核细胞分化伴随着PLSCR1表达的增加，而在用二甲基亚砜（DMSO）、丁酸钠或维生素D3分化的U937细胞中观察到PLSCR1表达的轻度或无升高。ATRA和PMA（而不是维生素D3或DMSO）的细胞分化导致蛋白激酶C（cid：1）（PKC（cid：1））的磷酸化，PKC（cid：1）特异性抑制剂rottlerin几乎消除了ATRA和PMA诱导的PLSCR1表达，而PKC（cid：1）组成性活性形式的异位表达直接增加PLSCR1表达。最后，用小干扰RNA降低PLSCR1表达抑制ATRA/PMA诱导的分化。综上所述，这些结果表明，作为PKC（cid：1）激活后诱导的蛋白质，PLSCR1是ATRA和PMA触发的白血病细胞分化所需的。（血。2004; 104：3731 - 3738）
phospholipid scramblase 1 (PLSCR1) based on its capacity to promote transbilayer movement of membrane phospholipids, subsequent studies also provided evidence for its role in cell proliferation, maturation, and apoptosis. In this report, we investigate the potential role of PLSCR1 in leukemic cell differentiation. We show that all- trans retinoic acid (ATRA), an effective differentiation-inducing agent of acute promyelocytic leukemic (APL) cells, can elevate PLSCR1 expression in ATRA-sensitiveAPL cells NB4 and HL60, but not in maturation-resistant NB4-LR1 cells. ATRA- and phorbol 12-myristate 13-ac-etate (PMA)–induced monocytic differentiation is accompanied by increased PLSCR1expression,whereasonlyaslight or no elevation of PLSCR1 expression is observed in U937 cells differentiated with dimethyl sulfoxide (DMSO), sodium butyrate, or vitamin D3. Cell differentiation with ATRA and PMA, but not with vitamin D3 or DMSO, results in phosphorylation of protein kinase C (cid:1) (PKC (cid:1) ), and the PKC (cid:1) -specific inhibitor rottlerin nearly eliminates the ATRA- and PMA-induced expression of PLSCR1, while ectopic expression of a constitutively active form of PKC (cid:1) directly increases PLSCR1 expression. Finally, decreasing PLSCR1 expression with small interfering RNA inhibits ATRA/PMA-induced differentiation. Taken together, these results suggest that as a protein induced upon PKC (cid:1) activation, PLSCR1 is required for ATRA- and PMA-triggered leukemic cell differentiation. (Blood. 2004;104:3731-3738)