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首页> 外文期刊>Molecular and Cellular Biology >Protein Tyrosine Phosphatase-Like A Regulates Myoblast Proliferation and Differentiation through MyoG and the Cell Cycling Signaling Pathway
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Protein Tyrosine Phosphatase-Like A Regulates Myoblast Proliferation and Differentiation through MyoG and the Cell Cycling Signaling Pathway

机译：像酪氨酸的磷酸酪氨酸磷酸酶一样，通过MyoG和细胞周期信号通路调节成肌细胞的增殖和分化。

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摘要

Protein tyrosine phosphatase-like A (PTPLa) has been implicated in skeletal myogenesis and cardiogenesis. Mutations in PTPLa correlated with arrhythmogenic right ventricular dysplasia in humans and congenital centronuclear myopathy with severe hypotonia in dogs. The molecular mechanisms of PTPLa in myogenesis are unknown. In this report, we demonstrate that PTPLa is required for myoblast growth and differentiation. The cells lacking PTPLa remained immature and failed to differentiate into mature myotubes. The repressed MyoG expression was responsible for the impaired myoblast differentiation. Meanwhile, impeded cell growth, with an obvious S-phase arrest and compromised G2/M transition, was observed in PTPLa-deficient myoblasts. Further study demonstrated that the upregulation of cyclin D1 and cyclin E2 complexes, along with a compromised G2/M transition due to the decreased CDK1 (cyclin-dependent kinase 1) activity and upregulated p21, contributed to the mutant cell S-phase arrest and eventually led to the retarded cell growth. Finally, the transcriptional regulation of the PTPLa gene was explored. We identified PTPLa as a new target gene of the serum response factor (SRF). Skeletal- and cardiac-muscle-specific SRF knockouts resulted in significant decreases in PTPLa expression, suggesting a conserved transcriptional regulation of the PTPLa gene in mice.
机译：蛋白酪氨酸磷酸酶样蛋白A（PTPLa）与骨骼肌发生和心脏发生有关。 PTPLa的突变与人的致心律失常性右心室发育异常和犬的先天性中心核肌病伴严重低渗有关。 PTPLa在肌发生中的分子机制尚不清楚。在本报告中，我们证明成肌细胞生长和分化需要PTPLa。缺乏PTPLa的细胞仍不成熟，无法分化为成熟的肌管。抑制的MyoG表达是成肌细胞分化受损的原因。同时，在缺乏PTPLa的成肌细胞中观察到细胞生长受阻，具有明显的S期停滞和受损的G 2 / M转变。进一步的研究表明，细胞周期蛋白D1和细胞周期蛋白E2复合体的上调，以及由于CDK1（细胞周期蛋白依赖性激酶1）活性降低和p21上调而导致的G 2 / M过渡受损，导致了细胞周期蛋白突变细胞S期停滞并最终导致细胞生长受阻。最后，探讨了PTPA1基因的转录调控。我们将PTPA1鉴定为血清反应因子（SRF）的新靶基因。骨骼肌和心肌特异性SRF基因敲除导致PTPLa表达显着降低，表明小鼠中PTPLa基因的保守转录调控。

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