Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis
Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis
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DOI：
10.1074/jbc.272.44.27521
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发表时间：
1997-10-31
影响因子：
4.8
通讯作者：
Fields, AP
中科院分区：
文献类型：
--
作者：
Murray, NR;Fields, AP
蛋白激酶 C (PHC) 同工酶在细胞功能中发挥着独特的作用。在人 K562 白血病细胞中，PKC α 对于细胞分化很重要，而 PKC β(II) 是增殖所必需的。在本报告中，我们评估了非典型 PKC 同种型 PKC iota 在 H562 白血病细胞生理学中的作用。用含有人 PKC iota cDNA 的表达质粒以有义或反义方向稳定转染 K562 细胞，以分别增加或降低细胞 PKC iota 水平。 PKC iota 的过表达或抑制表达对 K562 细胞的增殖能力及其对佛波醇肉豆蔻酸酯乙酸酯诱导的细胞抑制和巨核细胞分化的敏感性没有显着影响，表明 PKC iota 在这些过程中不起关键作用。相反，PKC iota 可以保护 K562 细胞免受药物诱导的凋亡，对大多数凋亡剂具有抗性的 K562 细胞在用该蛋白处理时会发生凋亡磷酸酶抑制剂冈田酸（OA）。 PKC iota 的过度表达导致对 OA 诱导的细胞凋亡的抵抗力增强，而抑制 PKC iota 表达则使细胞对 OA 诱导的细胞凋亡敏感。相关非典型 PKC zeta 的过度表达没有保护作用，表明该作用是同种型特异性的。PKC iota 还可以保护 K562 细胞免受紫杉醇诱导的细胞凋亡，表明它对细胞凋亡刺激发挥一般保护作用。这些数据支持 PKC iota 在白血病细胞存活中的作用。
Protein kinase C (PHC) isozymes play distinct roles in cellular function. In human K562 leukemia cells, PKC alpha is important for cellular differentiation and PKC beta(II) is required for proliferation. In this report, we assess the role of the atypical PKC isoform PKC iota in H562 leukemia cell physiology. K562 cells were stably transfected with expression plasmids containing the cDNA for human PKC iota in sense or antisense orientation to increase or decrease cellular PKC iota levels, respectively. Overexpression or inhibition of expression of PKC iota had no significant effect on the proliferative capacity of K562 cells nor their sensitivity to phorbol myristate acetate-induced cytostasis and megakaryocytic differentiation, suggesting that PKC iota does not play a critical role in these processes, Rather, PKC iota serves to protect K562 cells against drug-induced apoptosis, K562 cells, which are resistant to most apoptotic agents, undergo apoptosis when treated with the protein phosphatase inhibitor okadaic acid (OA). Overexpression of PKC iota leads to increased resistance to OA induced apoptosis whereas inhibition of PKC iota expression sensitizes cells to OA-induced apoptosis, Overexpression of the related atypical PKC zeta has no protective effect, demonstrating that the effect is isotype-specific, PKC iota also protects K562 cells against taxol-induced apoptosis, indicating that it plays a general protective role against apoptotic stimuli. These data support a role for PKC iota in leukemia cell survival.