Activation of p38alpha/beta MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo.

Activation of p38alpha/beta MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo.
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DOI:
10.1083/jcb.200608031
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发表时间:
2006-11-06
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Krauss RS
Krauss RS
中科院分区:
其他
文献类型:
--
作者:
Takaesu G;Kang JS;Bae GU;Yi MJ;Lee CM;Reddy EP;Krauss RS

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P38丝裂原活化蛋白激酶(MAPK)通路在细胞分化过程中起着重要作用,但在这一过程中它被激活的信号机制很大程度上是未知的。CDO是一个免疫球蛋白超家族成员,其功能是作为多蛋白细胞表面复合体的组成部分来促进肌肉发生。在这项研究中,我们报道了CDO胞内区与JLP相互作用,JLP是p38α/βMAPK途径的支架蛋白。在成肌细胞分化过程中,cdo、jlp和p38α/β形成复合体,cdo和jlp协同作用提高p38α/β的表达水平。来自cdo−/−小鼠的原代成肌细胞表现出分化程序缺陷,缺乏p38α/β活性,而活化形式的mkk6(p38的直接上游激活物)的表达拯救了cdo−/−细胞的分化能力。这些结果证明了细胞分化过程中一种新的信号机制:MAPK支架蛋白与细胞表面受体的相互作用。
The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cell differentiation, but the signaling mechanisms by which it is activated during this process are largely unknown. Cdo is an immunoglobulin superfamily member that functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that the Cdo intracellular region interacts with JLP, a scaffold protein for the p38α/β MAPK pathway. Cdo, JLP, and p38α/β form complexes in differentiating myoblasts, and Cdo and JLP cooperate to enhance levels of active p38α/β in transfectants. Primary myoblasts from Cdo −/− mice, which display a defective differentiation program, are deficient in p38α/β activity, and the expression of an activated form of MKK6 (an immediate upstream activator of p38) rescues the ability of Cdo −/− cells to differentiate. These results document a novel mechanism of signaling during cell differentiation: the interaction of a MAPK scaffold protein with a cell surface receptor.
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