Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal osteoblastic cells

Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal osteoblastic cells
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DOI:
10.1172/jci118432
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发表时间:
1996-01-15
影响因子:
15.9
通讯作者:
Manolagas, SC
Manolagas, SC
中科院分区:
医学1区
文献类型:
--
作者:
Bellido, T;Stahl, N;Manolagas, SC

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白细胞介素-6和白细胞介素-11介导的功能性受体复合物的组装(IL-6和IL-11)、白血病抑制因子(LIF)、制瘤素M(OSM)和睫状神经营养因子(CNTF),都涉及信号转导蛋白gp 130:IL-6和IL-11诱导gp 130的同源二聚化,而其余的则使gp 130与其他gp 130相关的β亚基异源二聚化。(IL-6,IL-11和CNTF)也需要不直接参与信号传导的特异性决定α亚基。我们已经在骨髓基质/成骨细胞谱系的细胞中寻找这些细胞因子的功能性受体复合物,使用β亚基的酪氨酸磷酸化作为检测测定。总体而言,鼠颅骨细胞、骨髓来源的鼠细胞系(+/+ LDA 11和MBA 13.2)以及鼠(MC 3 T3-E1)和人(MG-63)成骨细胞样细胞系显示了该受体家族的所有先前识别的α和β亚基。然而,单个细胞类型具有不同的α和β亚基星座。此外,与检查的其他细胞类型不同,MC 3 T3-E1细胞表达迄今未识别的gp 130形式; MG-63显示OSM受体的替代形式(II型)。这些研究结果表明,基质/成骨细胞的细胞因子亚家族的所有成员,共享的gp 130信号转导的行动的目标,并表明,不同的受体库可能会表达在不同阶段的分化这一谱系。
The functional receptor complexes assembled in response to interleukin-6 and -11 (IL-6 and IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF), all involve the signal transducer gp130: IL-6 and IL-11 induce homodimerization of gp130, while the rest heterodimerize gp130 with other gp130-related beta subunits, Some of these cytokines (IL-6, IL-11, and CNTF) also require a specificity-determining alpha subunit not directly involved in signaling. We have searched for functional receptor complexes for these cytokines in cells of the bone marrow stromal/osteoblastic lineage, using tyrosine phosphorylation of the beta subunits as a detection assay. Collectively, murine calvaria cells, bone marrow-derived murine cell lines (+/+LDA11 and MBA13.2), as well as murine (MC3T3-E1) and human (MG-63) osteoblast-like cell lines displayed all the previously recognized alpha and beta subunits of this family of receptors. However, individual cell types had different constellations of alpha and beta subunits, In addition and in difference to the other cell types examined, MC3T3-E1 cells expressed a heretofore unrecognized form of gp130; and MG-63 displayed an alternative form (type II) of the OSM receptor. These findings establish that stromal/osteoblastic cells are targets for the actions of all the members of the cytokine subfamily that shares the gp130 signal transducer; and suggest that different receptor repertoires may be expressed at different stages of differentiation of this lineage.