The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex
The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex
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DOI：
10.1006/jmbi.2001.5282
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发表时间：
2002-01-25
影响因子：
5.6
通讯作者：
Kallen, KJ
中科院分区：
文献类型：
--
作者：
Aasland, D;Oppmann, B;Kallen, KJ
To elucidate the function of the two cytokine-binding modules (CBM) of the leukemia inhibitory factor receptor (LIFR), receptor chimeras of LIFR and the interleukin-6 receptor (IL-6R) were constructed. Either the NH2- terminal (chimera RILLIFDeltaI) or the COOH-terminal LIFR CBM (chimera RILLIFDeltaII) were replaced by the structurally related CBM of the IL-6R which does not bind LIF. Chimera RILLIFDeltaI is functionally inactive, whereas RILLIFDeltaII binds LIF and mediates signalling as efficiently as the wild-type LIFR. Deletion mutants of the LIFR revealed that both the NH2-terminal CBM and the Ig-like domain of the LIFR are involved in LIF binding, presumably via the LIF site III epitope. The main function of the COOH-terminal CBM of the LIFR is to position the NH2-terminal CBM and the Ig-like domain, so that these can bind to LIF. In analogy to a recently published model of the IL-6R complex, a model of the active LIFR complex is suggested which positions the COOH-terminal CBM at LIF site I and the NH2-terminal CBM and the Ig-like domain at site III. An additional contact is postulated between the Ig-like domain of gp130 and the NH2-terminal CBM of the LIFR. (C) 2002 Academic Press.
