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首页> 外文期刊>Cytokine >Subtraction cloning and initial characterization of novel epo-immediate response genes.
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Subtraction cloning and initial characterization of novel epo-immediate response genes.

机译:减法克隆和新的epo立即反应基因的初步表征。

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Recent studies of erythropoietin (Epo) receptor signalling suggest that signals for mitogenesis, survival and differentiation are relayed efficiently by receptor forms lacking at least seven of eight cytoplasmic (phospho)tyrosine [(P)Y] sites for effector recruitment. While such receptor forms are known to activate Jak2 and a limited set of known immediate response genes (IRGs), the complex activities they exert predict the existence of additional target genes. To identify such targets, a minimal Epo receptor chimera was expressed in Epo-responsive erythroid SKT6 cells, and genes whose transcription is induced via this active receptor form were cloned by subtractive hybridization. Several known genes not previously linked to Epo signalling were discovered to be Epo IRGs including two which may further propagate Epo signals [Prl1 tyrosine phosphatase and receptor activator of of NFkappaB (Rank)], and three regulators of protein synthesis (EF1alpha, eIF3-p66 and Nat1). Several Epo IRGs were novel murine clones including FM2 and FM6 which proved to represent broadly expressed IRGs, and FM3 and FL10 which were induced primarily in haematopoietic cells. Interestingly, FL10 proved to correspond to a recently discovered regulator of yeast mating-type switching, and was induced by Epo in vivo. Thus, several new Epo signalling targets are described, which may modulate haematopoietic cell development. Copyright 2000 Academic Press.
机译:促红细胞生成素(Epo)受体信号转导的最新研究表明,有丝分裂发生,存活和分化的信号通过缺少至少8个胞质(磷酸)酪氨酸[(P)Y]位点中的7个用于效应子募集的受体形式有效传递。尽管已知此类受体形式可激活Jak2和一组有限的已知立即反应基因(IRG),但它们发挥的复杂活性可预测其他靶基因的存在。为了鉴定这样的靶标,在Epo应答性类红细胞SKT6细胞中表达最小的Epo受体嵌合体,并通过减性杂交克隆通过该活性受体形式诱导转录的基因。发现一些以前未与Epo信号相关的已知基因是Epo IRG,包括两个可进一步传播Epo信号的基因[Prl1酪氨酸磷酸酶和NFkappaB的受体激活剂(Rank)],以及三个蛋白质合成调节剂(EF1alpha,eIF3-p66和Nat1)。几个Epo IRGs是新颖的鼠类克隆,包括FM2和FM6,它们被证明代表了广泛表达的IRGs,以及FM3和FL10,它们主要在造血细胞中被诱导。有趣的是,FL10被证明与最近发现的酵母交配型转换调控因子相对应,并在体内被Epo诱导。因此,描述了几种新的Epo信号转导靶标,其可以调节造血细胞的发育。版权所有2000学术出版社。

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