Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene
Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene
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通过同源恒河猴 (Macaca mulatta) 基因的克隆和表达证明人白细胞介素 3 的物种特异性
DOI：
10.1182/blood.v76.11.2229.2229
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发表时间：
1990
期刊：
影响因子：
20.3
通讯作者：
G. Wagemaker
中科院分区：
文献类型：
--
作者：
H. Burger;R. W. Leen;L. Dorssers;N. Persoon;P. Lemson;G. Wagemaker
为了能够在灵长类物种中进行同源白细胞介素-3（IL-3）的临床前研究，我们分离了编码恒河猴IL-3（RhIL-3）的基因。该基因与人IL-3（hIL-3）基因的核苷酸序列同源性为92.9%。分离的RhIL-3基因编码一个143个氨基酸（aa）的前体多肽，9个C-末端残基短于人类蛋白质。与成熟蛋白（124个氨基酸）的同源性分别为80.5%和89.5%。人和RhIL-3编码序列的比较表明，大多数取代发生在氨基酸置换位点，表明IL-3蛋白的快速进化。在COS细胞中表达基因组片段后，构建了RhIL-3 cDNA，这使得能够大规模生产RhIL-3多肽。RhIL-3产生的地衣芽孢杆菌和纯化的同质性似乎是约100倍更有效地刺激恒河猴造血祖细胞比hIL-3，而RhIL-3和hIL-3显示出相当的刺激活性正常以及恶性人类造血细胞。因此，hIL-3的快速进化导致了单向的物种特异性，这很可能限制了hIL-3在猕猴物种中的体内作用。
To enable preclinical studies on homologous interleukin-3 (IL-3) in primate species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL-3). The nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a 143-amino acid (aa) precursor polypeptide, nine C-terminal residues shorter than the human protein. Protein homology was found to be 89.5% for the signal peptide (19 aa) and 80.5% for the mature protein (124 aa). Comparison of the human and RhIL-3 coding sequences showed that the majority of substitutions had occurred at amino acid replacement sites indicating a rapid evolution of the IL-3 protein. After expression of a genomic fragment in COS cells, RhIL-3 cDNA was constructed, which enabled large-scale production of the RhIL-3 polypeptide. RhIL-3 produced by Bacillus licheniformis and purified to homogeneity appeared to be approximately 100-fold more effective in stimulating Rhesus monkey hematopoietic progenitors than hIL-3, whereas RhIL-3 and hIL-3 showed comparable stimulatory activity on normal as well as malignant human hematopoietic cells. Thus, the rapid evolution of hIL-3 has resulted in a unidirectional species specificity, which most likely restricts the in vivo effects of hIL-3 in Macaca species.
IL-3 和促红细胞生成素对灵长类动物体内红细胞生成和 F 细胞形成的影响。
影响因子：
20.3
作者：
Umemura,T;al-Khatti,A;Donahue,RE;Papayannopoulou,T;Stamatoyannopoulos,G
通讯作者：
Stamatoyannopoulos,G
纯化的细菌合成的鼠多集落刺激因子 (IL-3) 对正常成年小鼠造血的影响。
影响因子：
20.3
作者：
Metcalf,D;Begley,CG;Johnson,GR;Nicola,NA;Lopez,AF;Williamson,DJ
通讯作者：
Williamson,DJ
集落刺激因子的分子生物学。
DOI：
--
发表时间：
1987
期刊：
Blood cells
影响因子：
--
作者：
Kaushansky,K
通讯作者：
Kaushansky,K