CLONING OF A MURINE IL-11 RECEPTOR ALPHA-CHAIN - REQUIREMENT FOR GP130 FOR HIGH-AFFINITY BINDING AND SIGNAL-TRANSDUCTION

CLONING OF A MURINE IL-11 RECEPTOR ALPHA-CHAIN - REQUIREMENT FOR GP130 FOR HIGH-AFFINITY BINDING AND SIGNAL-TRANSDUCTION
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DOI:
10.1002/j.1460-2075.1994.tb06802.x
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发表时间:
1994-10-17
期刊:
影响因子:
11.4
通讯作者:
WILLSON, TA
WILLSON, TA
中科院分区:
生物学1区
文献类型:
--
作者:
HILTON, DJ;HILTON, AA;WILLSON, TA

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成年小鼠肝脏cDNA文库中筛选的寡核苷酸对应于保守的WSXWS基序的促红细胞生成素受体家族。使用这种方法,cDNA克隆编码一种新的受体被分离。命名为NR 1的新受体在序列和预测结构上与IL-6受体的a链最相似,并且mRNA在3 T3-L1前脂肪细胞系和一系列原代组织中表达。NR 1在因子依赖性造血细胞系Ba/F3中的表达导致产生IL-11的低亲和力受体(Kd约为10 nM)。以高亲和力(Kd = 300-800 pM)结合IL-11的能力似乎需要NR 1和gp 130(IL-6、白血病抑制因子(LIF)、制瘤素M(OSM)和睫状神经营养因子(CNTF)受体的共同亚基)两者的共表达。NR 1和gp 130的表达也是Ba/F3细胞增殖和M1细胞响应IL-11进行巨噬细胞分化所必需的。
An adult mouse liver cDNA library was screened with oligonucleotides corresponding to the conserved WSXWS motif of the haemopoietin receptor family. Using this method, cDNA clones encoding a novel receptor were isolated. The new receptor, named NR1, was most similar in sequence and predicted structure to the a-chain of the IL-6 receptor and mRNA was expressed in the 3T3-L1 pre-adipocytic cell line and in a range of primary tissues. Expression of NR1 in the factor-dependent haemopoietic cell line Ba/F3 resulted in the generation of low affinity receptors for IL-11 (K-d approximate to 10 nM). The capacity to bind IL-11 with high affinity (K-d = 300-800 pM) appeared to require coexpression of both NR1 and gp130, the common subunit of the IL-6, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) receptors. The expression of both NR1 and gp130 was also necessary for Ba/F3 cells to proliferate and M1 cells to undergo macrophage differentiation in response to IL-11.