嵌合型促红细胞生成素-干扰素γ受体揭示了细胞内结构域在信号转导功能架构上的差异。
Chimeric erythropoietin-interferon gamma receptors reveal differences in functional architecture of intracellular domains for signal transduction.
作者信息
Muthukumaran G, Kotenko S, Donnelly R, Ihle J N, Pestka S
机构信息
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
出版信息
J Biol Chem. 1997 Feb 21;272(8):4993-9. doi: 10.1074/jbc.272.8.4993.
Binding of interferon gamma (IFN-gamma) causes oligomerization of the two interferon gamma receptor (IFN-gammaR) subunits, receptor chain 1 (IFN-gammaR1, the ligand-binding chain) and the second chain of the receptor (IFN-gammaR2), and causes activation of two Jak kinases (Jak1 and Jak2). In contrast, the erythropoietin receptor (EpoR) requires only one receptor chain and one Jak kinase (Jak2). Chimeras between the EpoR and the IFN-gammaR1 and IFN-gammaR2 chains demonstrate that the architecture of the EpoR and the IFN-gammaR complexes differ significantly. Although IFN-gammaR1 alone cannot initiate signal transduction, the chimera EpoR/gammaR1 (extracellular/intracellular) generates slight responses characteristic of IFN-gamma in response to Epo and the EpoR/gammaR1. EpoR/gammaR2 heterodimer is a fully functional receptor complex. The results demonstrate that the configuration of the extracellular domains influences the architecture of the intracellular domains.
γ干扰素（IFN-γ）的结合导致两个γ干扰素受体（IFN-γR）亚基发生寡聚化，即受体链1（IFN-γR1，配体结合链）和受体的第二条链（IFN-γR2），并导致两种Jak激酶（Jak1和Jak2）激活。相比之下，促红细胞生成素受体（EpoR）仅需要一条受体链和一种Jak激酶（Jak2）。EpoR与IFN-γR1和IFN-γR2链之间的嵌合体表明，EpoR和IFN-γR复合物的结构存在显著差异。虽然单独的IFN-γR1不能启动信号转导，但嵌合体EpoR/γR1（胞外/胞内）在响应促红细胞生成素（Epo）和EpoR/γR1时产生了IFN-γ特有的轻微反应。EpoR/γR2异二聚体是一种功能完全的受体复合物。结果表明，胞外结构域的构象会影响胞内结构域的结构。
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