GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit.
GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit.
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GM-CSF 与其受体结合诱导常见 β 亚基的寡聚化。
DOI：
10.1006/cyto.2000.0826
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
D'Andrea,RJ
中科院分区：
文献类型：
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作者：
McClure,BJ;Woodcock,JM;Harrison-Findik,D;Lopez,AF;D'Andrea,RJ
粒细胞-巨噬细胞集落刺激因子（GM-CSF）受体复合物的化学计量仍然没有解决。我们利用一种灵敏的受体同源二聚化功能试验，证明GM-CSF可诱导共同信号亚基hβc的二聚化。我们构建了一种嵌合细胞因子受体，其中hβcare的胞外和跨膜结构域融合到促红细胞生成素受体（EPO-R）的胞浆结构域。考虑到诱导EPO-R活化和促有丝分裂信号传导需要形成特异性同源二聚体复合物，我们推断EPO-R的胞质结构域可以用作功能性同源二聚体形成的高度敏感的报告基因。我们发现，在存在胞质截短的GM-CSF α亚基的情况下，hβc-EPO受体嵌合体在BaF-B 03中转导促有丝分裂信号以响应GM-CSF。这与GM-CSF结合后hβchomodimer的形成一致，并意味着配体刺激诱导含有hβchomodimer的高级复合物的形成。
The stoichiometry of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor complex is still unresolved. We have utilised a sensitive, functional assay for receptor homodimerisation to show that GM-CSF induces dimerisation of the common signalling subunit, hβc. We generated a chimeric cytokine receptor in which the extracellular and transmembrane domains of hβcare fused to the cytoplasmic domain of erythropoietin receptor (EPO-R). Given that to induce EPO-R activation and mitogenic signalling there is a requirement for formation of a specific homodimeric complex, we reasoned that the cytoplasmic domain of EPO-R could be utilised as a highly sensitive reporter for functional homodimer formation. We show that, in the presence of a cytoplasmically truncated GM-CSF α-subunit, the hβc–EPO receptor chimera transduces a mitogenic signal in BaF-B03 in response to GM-CSF. This is consistent with formation of a hβchomodimer following GM-CSF binding and implies that ligand stimulation induces formation of a higher order complex that contains the hβchomodimer.