Signaling by Kit has been extensively studied in hematopoietic cells and is essential for the survival, proliferation and maintenance of hematopoietic stem and progenitor cells. In addition to the activation of intrinsic signaling pathways, Kit has been shown to interact with lineage-restricted type I cytokine receptors and produce cross signals, e.g. erythropoietin receptor, interleukin-7 receptor (IL-7R), IL-3R. Based on the earlier studies, we hypothesize that Kit activate other type I cytokine receptors in a cell-specific manner and execute cell-specific function. To investigate other Kit-activated receptors, we tested Kit and IL-4R cross-receptor activation in murine bone-marrow-derived mast cells, which express both Kit and IL-4R at the surface level. Kit upon activation by Kit ligand (KL), activated IL-4Rα, γC , and signal transducer and activator of transcription 6 independent of its cognate ligand IL-4. Though KL and IL-4 are individually mitogenic, combinations of KL and IL-4 synergistically promoted mast cell proliferation. Furthermore, inhibition of lipid raft formation by methyl-β-cyclodextrin resulted in loss of synergistic proliferation. Together the data suggest IL-4R as a novel Kit-activated receptor. Such cross-receptor activations are likely to be a universal mechanism of Kit signaling in hematopoiesis.

中文翻译：

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该试剂盒可在小鼠肥大细胞中激活白介素4受体和效应子信号转导子以及转录激活因子6，而与其相关配体无关。

Kit的信号转导已经在造血细胞中进行了广泛的研究，对于造血干细胞和祖细胞的存活，增殖和维持至关重要。除激活内在信号传导途径外，Kit还显示与谱系受限的I型细胞因子受体相互作用并产生交叉信号，例如促红细胞生成素受体，白介素7受体（IL-7R），IL-3R。基于较早的研究，我们假设Kit可以以细胞特异性方式激活其他I型细胞因子受体并执行细胞特异性功能。为了研究其他Kit激活的受体，我们在小鼠骨髓衍生的肥大细胞中测试了Kit和IL-4R交叉受体的激活，该肥大细胞在表面水平上均表达Kit和IL-4R。通过Kit配体（KL），活化的IL-4Rα，γC激活后的Kit 信号转导子和转录激活子6与其同源配体IL-4无关。尽管KL和IL-4分别是促有丝分裂的，但是KL和IL-4的组合可协同促进肥大细胞增殖。此外，甲基-β-环糊精对脂质筏形成的抑制导致协同增殖的丧失。数据一起提示IL-4R是一种新型的Kit活化受体。这种交叉受体激活可能是造血过程中Kit信号传导的普遍机制。数据一起提示IL-4R是一种新型的Kit活化受体。此类交叉受体激活可能是造血过程中Kit信号传导的普遍机制。数据一起提示IL-4R是一种新型的Kit活化受体。此类交叉受体激活可能是造血过程中Kit信号传导的普遍机制。