Truncated activin type II receptor inhibits erythroid differentiation in K562 cells
Truncated activin type II receptor inhibits erythroid differentiation in K562 cells
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截短的激活素 II 型受体抑制 K562 细胞红系分化
DOI：
--
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发表时间：
2000
影响因子：
4
通讯作者：
John Yu
中科院分区：
文献类型：
--
作者：
Fang Liu;L. Shao;John Yu
两种受体丝氨酸/苏氨酸激酶（I型和II型）已被鉴定为信号转导激活素受体。我们研究了使用II型受体的显性负突变体抑制K562细胞中激活素A依赖性分化的可能性。构建表达缺乏胞质激酶结构域的激活素II型截短受体（ActRIIa）的载体。由于激活素I型和II型受体形成用于信号传导的异聚复合物，突变体受体竞争与内源性受体结合，因此以显性负性方式起作用。用ActRIIa稳定转染K562细胞，并扩增独立克隆。如聚合酶链反应所示，截短的cDNA整合到转染子的基因组中;截短的受体的表面表达通过与125 I-激活素A的亲和交联来显示。在野生型K562细胞中，激活素A诱导红系分化，细胞开始表达血红蛋白。在表达ActRIIa的转染细胞中，在用激活素A培养后，红系分化的诱导被废除，并且少于10%的细胞是含血红蛋白的细胞。用野生型II型受体进一步转染挽救了这些转染子的突变体表型，表明ActRIIa的作用是显性负性的。此外，在体外II型受体的胞质激酶结构域的磷酸化证实了受体的这一部分的自磷酸化。因此，体外红系分化的诱导是通过细胞表面激活素受体介导的，并且干扰该受体信号传导抑制K562细胞中的该分化过程。J.细胞。78：24-33，2000.© 2000 Wiley利斯公司
Two receptor serine/threonine kinases (types I and II) have been identified as signaling transducing activin receptors. We studied the possibility of inhibiting activin A‐dependent differentiation in K562 cells, using a dominant negative mutant of type II receptor. A vector was constructed expressing activin type II truncated receptor (ActRIIa) that lacks the cytoplasmic kinase domain. Since activin type I and II receptors form heteromeric complexes for signaling, the mutant receptors compete for binding to endogenous receptors, hence acting in a dominant negative fashion. K562 cells were stably transfected with ActRIIa, and independent clones were expanded. The truncated cDNA was integrated into the genome of the transfectants, as shown by polymerase chain reaction; and the surface expression of truncated receptors was shown by affinity cross‐linking with 125I‐activin A. In wild‐type K562 cells, activin A induced erythroid differentiation and cells started to express hemoglobins. In transfected cells expressing ActRIIa, the induction of erythroid differentiation was abrogated and less than 10% of cells were hemoglobin‐containing cells after culture with activin A. Further transfection with wild‐type type II receptors rescued the mutant phenotype of these transfectants, indicating that the effect of ActRIIa is dominant negative. In addition, phosphorylation of the cytoplasmic kinase domain of the type II receptor in vitro confirms the autophosphorylation of this portion of the receptor. Therefore, induction of erythroid differentiation in vitro is mediated through the cell surface activin receptor, and interference with this receptor signaling inhibits this process of differentiation in K562 cells. J. Cell. Biochem. 78:24–33, 2000. © 2000 Wiley‐Liss, Inc.
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DOI：
10.1210/endo.136.12.7588300
发表时间：
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期刊：
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