Protein kinase C in erythroid and megakaryocytic differentiation: possible role in lineage determination.

Protein kinase C in erythroid and megakaryocytic differentiation: possible role in lineage determination.
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红细胞和巨核细胞分化中的蛋白激酶 C:在谱系测定中的可能作用。

DOI:
10.1016/s0167-4889(97)00051-7
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发表时间:
1997
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Schwartz,BS
Schwartz,BS
中科院分区:
--
文献类型:
--
作者:
Lumelsky,NL;Schwartz,BS

文献摘要

被引文献

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正常人造血祖细胞的红系分化受到佛波酯、12-肉豆蔻酸酯 13-乙酸酯 (PMA) 的显着抑制,佛波酯是一种已知可激活丝氨酸-苏氨酸激酶类蛋白激酶 C (PKC) 的药物。这种抑制伴随着巨核细胞分化的增强,如巨核细胞特异性 mRNA 和蛋白质的表达所证明的那样。 PMA 的这些作用可被 PKC 的两种特异性拮抗剂逆转。对从不含PMA的培养物转移至含有PMA的培养物的单菌落的分析表明,在该系统中,PMA直接对可能已经启动向红细胞分化途径进展的细胞发挥巨核细胞分化活性。这些结果表明,PKC 活性的调节在红细胞和巨核细胞分化中发挥作用,并且可能在正常血细胞发育过程中构成这些途径之间的重要选择性信号。
Erythroid differentiation of normal human hematopoietic progenitor cells was drastically inhibited by phorbol ester, 12-myristate 13-acetate (PMA), an agent known to activate the class of serine-threonine kinases, protein kinase C (PKC). This inhibition was accompanied by augmented megakaryocytic differentiation as demonstrated by expression of megakaryocyte-specific mRNAs and proteins. These effects of PMA were reversed by two specific antagonists of PKC. Analysis of single colonies transferred from cultures not containing PMA to PMA-containing cultures indicated that, in this system, PMA exerts megakaryocytic differentiating activity directly on cells which may have already initiated a progression toward the erythroid pathway of differentiation. These results suggest that modulation of PKC activity plays a role in erythroid and megakaryocytic differentiation, and may constitute an important selective signal between these pathways during normal blood cell development.