Association of active extracellular signal-regulated protein kinase with paired helical filaments of inclusion-body myositis muscle suggests its role in inclusion-body myositis tau phosphorylation.
Association of active extracellular signal-regulated protein kinase with paired helical filaments of inclusion-body myositis muscle suggests its role in inclusion-body myositis tau phosphorylation.
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活性细胞外信号调节蛋白激酶与包涵体肌炎肌肉的成对螺旋丝的关联表明其在包涵体肌炎 tau 磷酸化中的作用。
DOI：
10.1016/s0002-9440(10)65056-0
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Askanas,V
中科院分区：
文献类型：
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作者：
Wilczynski,GM;Engel,WK;Askanas,V
通过对6例包涵体肌炎（IBM）和14例对照组患者肌肉活检组织中ERK活性磷酸化形式进行免疫染色，研究了ERK在IBM发病机制中的可能作用。80%至90%的IBM空泡化肌纤维含有明确的ERK免疫反应性包涵体，这些包涵体通过光学显微镜共定位，其中70%至80%的纤维中含有磷酸化tau蛋白。免疫电镜共定位ERK的小无定形簇相邻的肌纤维双螺旋丝。强ERK免疫反应性也存在于所有人类神经肌肉接头的突触后结构域。我们的研究表明：1）ERK，一种信号转导，可能在IBM发病机制中发挥作用，包括参与IBM tau蛋白的病理性磷酸化; 2）信号转导异常可能是IBM致病级联反应的一个组成部分。我们的新免疫定位ERK在人类神经肌肉接头的突触后结构域支持的作用，在转录的连接蛋白基因。位于IBM纤维的非连接区的ERK可能是已知的连接蛋白病理性上调的基础。
The possible role of extracellular signal-regulated kinase (ERK) in the pathogenesis of inclusion-body myositis (IBM) was investigated by immunostaining the active phosphorylated form of ERK in muscle biopsies of six IBM and 14 control patients. Between 80% and 90% of IBM vacuolated muscle fibers contained well-defined ERK-immunoreactive inclusions, which were co-localized by light microscopy, with phosphorylated tau in 70 to 80% of those fibers. Immunoelectronmicroscopy colocalized ERK to small amorphous tufts adjacent to the muscle fiber paired-helical filaments. Strong ERK immunoreactivity was also present at the postsynaptic domain of all human neuromuscular junctions. Our study suggests 1) that ERK, a signal transducer, might play a role in IBM pathogenesis, including participation in the pathological phosphorylation of IBM tau; and 2) that signal transduction abnormalities may be a component of the IBM pathogenic cascade. Our novel immunolocalization of ERK at the postsynaptic domain of human neuromuscular junctions supports a role in transcription of junctional-protein genes. The ERK localized in nonjunctional regions of IBM fibers may underlie the known pathological up-regulation of junctional proteins there.