Gearing D P, Ziegler S F, Comeau M R, Friend D, Thoma B, Cosman D, Park L, Mosley B
Immunex Research and Development Corporation, Seattle, WA 98101.
Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1119-23. doi: 10.1073/pnas.91.3.1119.
Specific low-affinity receptors for leukemia inhibitory factor (LIF), oncostatin M (OSM; gp130), and ciliary neurotrophic factor (CNTF; receptor alpha, CNTFR alpha) may be utilized in various combinations to generate high-affinity binding sites and signal transduction. We have tested the ability of combinations of these receptors to transduce a proliferative signal in BAF-B03 cells. Coexpression of the LIF receptor and gp130 in these cells conferred high-affinity LIF and OSM binding and responsiveness to LIF and OSM. These cells also responded to CNTF in the absence of detectable binding. The further addition of CNTFR alpha conferred high-affinity CNTF binding and enhanced responsiveness to CNTF but did not modify responses to LIF or OSM. Coexpression of LIF receptor and CNTFR alpha resulted in a nonfunctional high-affinity binding site. These data are consistent with a role for the CNTFR alpha in enhancing CNTF action but the CNTFR alpha is not absolutely required for CNTF action and suggest a wider range of targets for CNTF.
白血病抑制因子(LIF)、抑瘤素M(OSM;gp130)和睫状神经营养因子(CNTF;受体α,CNTFRα)的特异性低亲和力受体可以以各种组合形式被利用,以产生高亲和力结合位点和信号转导。我们已经测试了这些受体组合在BAF - B03细胞中传导增殖信号的能力。在这些细胞中LIF受体和gp130的共表达赋予了高亲和力的LIF和OSM结合能力以及对LIF和OSM的反应性。这些细胞在没有可检测到的结合的情况下也对CNTF有反应。进一步添加CNTFRα赋予了高亲和力的CNTF结合能力并增强了对CNTF的反应性,但没有改变对LIF或OSM的反应。LIF受体和CNTFRα的共表达导致了一个无功能的高亲和力结合位点。这些数据与CNTFRα在增强CNTF作用方面的作用一致,但CNTF作用并不绝对需要CNTFRα,并提示了CNTF更广泛的作用靶点。