CaM kinase IV regulates lineage commitment and survival of erythroid progenitors in a non-cell-autonomous manner.
CaM kinase IV regulates lineage commitment and survival of erythroid progenitors in a non-cell-autonomous manner.
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CAM激酶IV调节以非细胞自主方式的骨o祖祖细胞的谱系承诺和存活。
DOI：
10.1083/jcb.151.4.811
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发表时间：
2000-11-13
期刊：
影响因子：
--
通讯作者：
Christian JL
中科院分区：
文献类型：
--
作者：
Wayman GA;Walters MJ;Kolibaba K;Soderling TR;Christian JL
钙调素依赖性蛋白激酶IV （CaM KIV）的发育功能尚未被研究。在这里，我们发现CaM KIV转录本在胚胎发生过程中广泛分布，并且CaM KIV活性的严格调控对于正常的原始红细胞生成至关重要。CaM KIV活性上调或抑制的爪蟾胚胎表明造血前体得到了适当的指定，但很少产生成熟的红细胞。明显的细胞缺陷是红细胞丧失的基础：抑制CaM KIV活性导致造血前体以牺牲红细胞分化为代价向髓细胞分化，另一方面，CaM KIV的组成性激活诱导红细胞前体经历凋亡细胞死亡。即使CaM KIV活性仅在不参与红系谱系的细胞中被错误调节，也可以观察到这些血液缺陷。因此，在非造血组织中适当调节CaM KIV活性对于产生外部信号至关重要，这些信号使造血干细胞能够向红细胞分化并支持红细胞前体的存活。
Developmental functions of calmodulin-dependent protein kinase IV (CaM KIV) have not been previously investigated. Here, we show that CaM KIV transcripts are widely distributed during embryogenesis and that strict regulation of CaM KIV activity is essential for normal primitive erythropoiesis. Xenopus embryos in which CaM KIV activity is either upregulated or inhibited show that hematopoietic precursors are properly specified, but few mature erythrocytes are generated. Distinct cellular defects underlie this loss of erythrocytes: inhibition of CaM KIV activity causes commitment of hematopoietic precursors to myeloid differentiation at the expense of erythroid differentiation, on the other hand, constitutive activation of CaM KIV induces erythroid precursors to undergo apoptotic cell death. These blood defects are observed even when CaM KIV activity is misregulated only in cells that do not contribute to the erythroid lineage. Thus, proper regulation of CaM KIV activity in nonhematopoietic tissues is essential for the generation of extrinsic signals that enable hematopoietic stem cell commitment to erythroid differentiation and that support the survival of erythroid precursors.
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