Shanafelt A B, Miyajima A, Kitamura T, Kastelein R A
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
EMBO J. 1991 Dec;10(13):4105-12. doi: 10.1002/j.1460-2075.1991.tb04987.x.
Transduction of the biological effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) requires the interaction of each cytokine with at least two cell surface receptor components, one of which is shared between these two cytokines. A strategy is presented that allowed us to identify receptor binding determinants in GM-CSF and IL-5. Mixed species (human and mouse) receptors were used to locate unique receptor binding domains on a series of human-mouse hybrid GM-CSF and IL-5 cytokines. Results show that the interaction of these two cytokines with the shared subunit of their high affinity receptor complexes is governed by a very small part of their peptide chains. The presence of a few key residues in the amino-terminal alpha-helix of each ligand is sufficient to confer specificity to the interaction. Comparison with other cytokines suggests that the amino-terminal helix of many of these proteins may contain the recognition element for the formation of high affinity binding sites with the alpha subunit of their multi-component receptors.
粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-5（IL-5）的生物学效应转导需要每种细胞因子与至少两种细胞表面受体成分相互作用，其中一种受体成分是这两种细胞因子所共有的。本文提出了一种策略，使我们能够鉴定GM-CSF和IL-5中的受体结合决定簇。利用混合物种（人和小鼠）受体在一系列人-鼠杂交GM-CSF和IL-5细胞因子上定位独特的受体结合域。结果表明，这两种细胞因子与其高亲和力受体复合物的共享亚基之间的相互作用由其肽链中非常小的一部分所决定。每种配体氨基末端α-螺旋中几个关键残基的存在足以赋予相互作用特异性。与其他细胞因子的比较表明，许多这些蛋白质的氨基末端螺旋可能包含与其多组分受体α亚基形成高亲和力结合位点的识别元件。
