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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ganglioside GM1 binds to the Trk protein and regulates receptor function.
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Ganglioside GM1 binds to the Trk protein and regulates receptor function.

机译：神经节苷脂GM1与Trk蛋白结合并调节受体功能。

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摘要

Several lines of evidence have suggested that ganglioside GM1 stimulates neuronal sprouting and enhances the action of nerve growth factor (NGF), but its precise mechanism is yet to be elucidated. We report here that GM1 directly and tightly associates with Trk, the high-affinity tyrosine kinase-type receptor for NGF, and strongly enhances neurite outgrowth and neurofilament expression in rat PC12 cells elicited by a low dose of NGF that alone is insufficient to induce neuronal differentiation. The potentiation of NGF activity by GM1 appears to involve tyrosine-autophosphorylation of Trk, which contains intrinsic tyrosine kinase activity that has been localized to the cytoplasmic domain. In the presence of GM1 in culture medium, there is a > 3-fold increase in NGF-induced autophosphorylation of Trk as compared with NGF alone. We also found that GM1 could directly enhance NGF-activated autophosphorylation of immunoprecipitated Trk in vitro. Monosialoganglioside GM1, but not polysialogangliosides, is tightly associated with immunoprecipitated Trk. Furthermore, such tight association of GM1 with Trk appears to be specific, since a similar association was not observed with other growth factor receptors, such as low-affinity NGF receptor (p75NGR) and epidermal growth factor receptor (EGFR). Thus, these results strongly suggest that GM1 functions as a specific endogenous activator of NGF receptor function, and these enhanced effects appear to be due, at least in part, to tight association of GM1 with Trk.
机译：有几条证据表明，神经节苷脂GM1刺激神经元发芽并增强神经生长因子（NGF）的作用，但其确切机制尚待阐明。我们在这里报告，GM1与Nrk的高亲和力酪氨酸激酶型受体Trk直接紧密结合，并强烈增强了低剂量NGF诱导的大鼠PC12细胞中神经突的长出和神经丝的表达，而单剂量不足以诱导神经元差异化。 GM1增强NGF活性似乎涉及Trk的酪氨酸自磷酸化，Trk包含已定位于细胞质结构域的内在酪氨酸激酶活性。在培养基中存在GM1时，与单独的NGF相比，NGF诱导的Trk自磷酸化增加> 3倍。我们还发现GM1可以在体外直接增强NGF激活的免疫沉淀Trk的自磷酸化。单唾液酸神经节苷脂GM1，而不是多唾液酸神经节苷脂，与免疫沉淀的Trk紧密相关。此外，GM1与Trk的这种紧密联系似乎是特异性的，因为未与其他生长因子受体（如低亲和力NGF受体（p75NGR）和表皮生长因子受体（EGFR））观察到相似的联系。因此，这些结果强烈表明GM1充当NGF受体功能的特定内源性激活剂，而这些增强的作用似乎至少部分是由于GM1与Trk的紧密结合所致。

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