Nakano S, Shinde A, Ito H, Ito H, Kusaka H
Department of Neurology, Kansai Medical University, Moriguchi-city, Japan.
Neurology. 2003 Aug 12;61(3):322-6. doi: 10.1212/01.wnl.0000076479.29079.10.
To investigate alterations in protein kinases and phosphatases that regulate the activity of mitogen activated protein kinase (MAPK) in sporadic inclusion body myositis (IBM).
In vacuolated fibers in IBM, several studies reported upregulation of the extracellular regulated kinase (ERK) subclass of MAPK family. Whereas MAPK kinases (MKK) activate MAPK, MAPK phosphatases (MKP) inactivate MAPK. MKP-1 is involved in muscle fiber differentiation and it is downregulated during myotube formation.
Immunolocalization of MKK1 through MKK4 and MKP-1 to MKP-3 was tested in muscle specimens from 10 patients with IBM and controls.
In IBM, strong and focal deposits of MKP-1 were observed in vacuolated fibers. The MKP-1-positive deposits were colocalized with ERK. MKP-2, MKP-3, and MKK were not associated with vacuolated fibers.
In IBM, MKP-1 is abnormally induced in vacuolated fibers probably to inactivate ERK. Although direct activators other than those tested in the current study might induce ERK, the absence of activation of MKK suggests that the aggregation of ERK protein itself causes the seeming upregulation of the protein kinase in IBM. Like ERK and its nuclear substrate, MKP-1 is an enzyme that forms aggregates in vacuolated fibers and is involved in myogenesis.
研究散发性包涵体肌炎（IBM）中调节丝裂原活化蛋白激酶（MAPK）活性的蛋白激酶和磷酸酶的变化。
在IBM的空泡化纤维中，多项研究报道了MAPK家族的细胞外调节激酶（ERK）亚类上调。MAPK激酶（MKK）激活MAPK，而MAPK磷酸酶（MKP）使MAPK失活。MKP-1参与肌纤维分化，在肌管形成过程中表达下调。
对10例IBM患者和对照组的肌肉标本进行MKK1至MKK4以及MKP-1至MKP-3的免疫定位检测。
在IBM中，空泡化纤维中观察到MKP-1有强烈的局灶性沉积。MKP-1阳性沉积物与ERK共定位。MKP-2、MKP-3和MKK与空泡化纤维无关。
在IBM中，空泡化纤维中异常诱导MKP-1可能是为了使ERK失活。尽管除本研究检测的激活剂外的其他直接激活剂可能诱导ERK，但MKK未被激活表明ERK蛋白本身的聚集导致了IBM中蛋白激酶看似上调。与ERK及其核底物一样，MKP-1是一种在空泡化纤维中形成聚集体并参与肌生成的酶。
