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首页> 外文期刊>Molecular and Cellular Biology >GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases.
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GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases.

机译：GTPase缺乏的G alpha 16和G alpha q诱导PC12细胞分化和cJun NH2末端激酶的持续活化。

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Persistent stimulation of specific protein kinase pathways has been proposed as a key feature of receptor tyrosine kinases and intracellular oncoproteins that signal neuronal differentiation of rat pheochromocytoma (PC12) cells. Among the protein serine/threonine kinases identified to date, the p42/44 mitogen-activated protein (MAP) kinases have been highlighted for their potential role in signalling PC12 cell differentiation. We report here that retrovirus-mediated expression of GTPase-deficient, constitutively active forms of the heterotrimeric Gq family members, G alpha qQ209L and G alpha 16Q212L, in PC12 cells induces neuronal differentiation as indicated by neurite outgrowth and the increased expression of voltage-dependent sodium channels. Differentiation was not observed after cellular expression of GTPase-deficient forms of alpha i2 or alpha 0, indicating selectivity for the Gq family of G proteins. As predicted, overexpression of alpha qQ209L and alpha 16Q212L constitutively elevated basal phospholipase C activity approximately 10-fold in PC12 cells. Significantly, little or no p42/44 MAP kinase activity was detected in PC12 cells differentiated with alpha 16Q212L or alpha qQ209L, although these proteins were strongly activated following expression of constitutively active cRaf-1. Rather, a persistent threefold activation of the cJun NH2-terminal kinases (JNKs) was observed in PC12 cells expressing alpha qQ209L and alpha 16Q212L. This level of JNK activation was similar to that achieved with nerve growth factor, a strong inducer of PC12 cell differentiation. Supportive of a role for JNK activation in PC12 cell differentiation, retrovirus-mediated overexpression of cJun, a JNK target, in PC12 cells induced neurite outgrowth. The results define a p42/44 MAP kinase-independent mechanism for differentiation of PC12 cells and suggest that persistent activation of the JNK members of the proline-directed protein kinase family by GTPase-deficient G alpha q and G alpha 16 subunits is sufficient to induce differentiation of PC12 cells.
机译：持久性刺激特定的蛋白激酶途径已被提议为受体酪氨酸激酶和细胞内癌蛋白的关键特征，这些信号提示大鼠嗜铬细胞瘤（PC12）细胞的神经元分化。在迄今确定的蛋白质丝氨酸/苏氨酸激酶中，p42 / 44丝裂原活化蛋白（MAP）激酶因其在PC12细胞分化信号中的潜在作用而被强调。我们在这里报告说，逆转录病毒介导的PC12细胞中异源三聚体Gq家族成员Galpha qQ209L和G alpha 16Q212L的GTPase缺陷型，组成型活性形式的表达诱导神经元分化，如神经突向外生长和电压依赖性表达的增加钠通道。细胞表达GTPase缺陷型的alpha i2或alpha 0后未观察到分化，表明对G蛋白的Gq家族具有选择性。如所预测的，αqQ209L和α16Q212L的过表达在PC12细胞中组成性地提高了基础磷脂酶C的活性约10倍。显着地，在用α16Q212L或αqQ209L分化的PC12细胞中检测到很少或没有p42 / 44 MAP激酶活性，尽管这些蛋白在组成型活性cRaf-1表达后被强烈激活。而是，在表达αqQ209L和α16Q212L的PC12细胞中观察到cJun NH2末端激酶（JNK）的持续三倍激活。此JNK激活水平与神经生长因子（一种PC12细胞分化的强诱导剂）所达到的水平相似。在PC12细胞诱导的神经突生长中，逆转录病毒介导的cJun cJun的过表达支持了JNK在PC12细胞分化中的作用。结果定义了p42 / 44 MAP激酶非依赖性的PC12细胞分化机制，并表明由GTPase缺失的G alpha q和G alpha 16亚基持续激活脯氨酸定向蛋白激酶家族的JNK成员足以诱导PC12细胞的分化。

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