PKN2 and Cdo interact to activate AKT and promote myoblast differentiation.
PKN2 and Cdo interact to activate AKT and promote myoblast differentiation.
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DOI：
10.1038/cddis.2016.296
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发表时间：
2016-10-20
影响因子：
9
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中科院分区：
文献类型：
--
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骨骼肌发生是由多种信号通路协调的，这些信号通路控制细胞粘附/迁移、存活和分化，并伴随着肌肉特异性基因表达。细胞表面蛋白Cdo通过激活p38 MAPK和AKT参与细胞接触介导的促肌原性信号。蛋白激酶C相关激酶2（PKN 2/PRK 2）参与调节各种生物过程，包括细胞迁移、粘附和死亡。已显示其与AKT相互作用并抑制AKT，从而诱导细胞死亡。这使我们研究PKN 2在骨骼肌发生中的作用以及PKN 2和Cdo之间的串扰。与Cdo一样，PKN 2在分化过程中在C2 C12成肌细胞中上调，并且在由shRNA引起的Cdo耗尽或在整合素非依赖性基质上培养的细胞中下调。PKN 2水平的下降导致成肌细胞分化过程中AKT活化减少。一致的是，PKN 2过表达增强C2 C12成肌细胞分化，而PKN 2缺失损害它，而不影响细胞存活。PKN 2通过其C-末端区域与Cdo、APPL 1和AKT形成复合物，并且这种相互作用似乎对于诱导AKT活性以及成肌细胞分化是重要的。此外，PKN 2通过介导BAF 60 c和MyoD向肌细胞生成素启动子的募集来增强MyoD应答报告活性。总之，PKN 2在成肌细胞分化过程中细胞粘附介导的AKT活化中具有关键作用。
Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death. This led us to investigate the role of PKN2 in skeletal myogenesis and the crosstalk between PKN2 and Cdo. Like Cdo, PKN2 was upregulated in C2C12 myoblasts during differentiation and decreased in cells with Cdo depletion caused by shRNA or cultured on integrin-independent substratum. This decline of PKN2 levels resulted in diminished AKT activation during myoblast differentiation. Consistently, PKN2 overexpression-enhanced C2C12 myoblast differentiation, whereas PKN2-depletion impaired it, without affecting cell survival. PKN2 formed complexes with Cdo, APPL1 and AKT via its C-terminal region and this interaction appeared to be important for induction of AKT activity as well as myoblast differentiation. Furthermore, PKN2-enhanced MyoD-responsive reporter activities by mediating the recruitment of BAF60c and MyoD to the myogenin promoter. Taken together, PKN2 has a critical role in cell adhesion-mediated AKT activation during myoblast differentiation.
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影响因子：
3.3
作者：
Bae GU;Lee JR;Kim BG;Han JW;Leem YE;Lee HJ;Ho SM;Hahn MJ;Kang JS
通讯作者：
Kang JS
影响因子：
3.7
作者：
Lachmann S;Jevons A;De Rycker M;Casamassima A;Radtke S;Collazos A;Parker PJ
通讯作者：
Parker PJ
影响因子：
4.8
作者：
Balendran, A;Biondi, RM;Alessi, DR
通讯作者：
Alessi, DR
影响因子：
11.4
作者：
Kang, JS;Mulieri, PJ;Krauss, RS
通讯作者：
Krauss, RS
影响因子：
50.3
作者：
Donovan, S;See, W;Shannon, KM
通讯作者：
Shannon, KM