Specific protein kinase C isoforms are required for rod photoreceptor differentiation.
Specific protein kinase C isoforms are required for rod photoreceptor differentiation.
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DOI：
10.1523/jneurosci.2578-11.2011
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发表时间：
2011-12-14
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影响因子：
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通讯作者：
Barnstable CJ
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文献类型：
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作者：
Pinzon-Guzman C;Zhang SS;Barnstable CJ
蛋白激酶C（PKC）家族的酶通过磷酸化大多数细胞类型中许多蛋白质的丝氨酸和苏氨酸残基来调节细胞生理学。在这里，我们已经确定了PKC-β1和PKC-γ的亚型是必不可少的视杆细胞分化在小鼠视网膜。使用离体视网膜外植体，我们发现佛波醇酯12-肉豆蔻酸酯13-乙酸酯（PMA）和胰岛素样生长因子1（IGF 1）诱导视杆分化，定义视蛋白或Crx的表达，在PKC依赖的方式在未经处理的外植体杆发展的前几天。PKC-β1和PKC-γ在分化后期与PCNA和STAT 3阳性祖细胞共定位。药理学或遗传抑制任一异构体导致部分减少杆的外观，而删除两个异构体导致其完全不存在。此外，通过激活PKC观察到STAT 3酪氨酸磷酸化的显著下降，而抑制PKC导致磷酸化的STAT 3沿着具有延长的PCNA表达的祖细胞的延迟的细胞周期退出而增加。在成人视网膜中，IGF 1激活PI-3激酶（PI 3 K），但在新生儿视网膜中，其作用与PI 3 K抑制剂的作用相同。这些数据揭示了一种新的信号级联，协调和调节杆分化通过特定的PKC亚型在哺乳动物。
The protein kinase C (PKC) family of enzymes regulates cell physiology through phosphorylation of serine and threonine residues of many proteins in most cell types. Here we have identified PKC-β1 and PKC-γ as isoforms are essential for rod photoreceptor differentiation in mouse retinas. Using ex vivo retinal explants we found that phorbol ester 12-myristate 13-acetate (PMA) and insulin-like growth factor 1 (IGF1) induced rod differentiation, as defined by opsin or Crx expression, in a PKC-dependent manner days ahead of rod development in untreated explants. PKC-β1 and PKC-γ were co-localized with PCNA- and STAT3-positive progenitors through the later differentiation period. Pharmacological or genetic inhibition of either isoform resulted in partial reduction in appearance of rods, whereas removing both isoforms resulted in their complete absence. Furthermore, a significant decline of STAT3 tyrosine phosphorylation was observed by activation of PKC, while inhibition of PKC resulted in an increase of phosphorylated STAT3 along with a delayed cell cycle exit of progenitors with prolonged PCNA expression. In adult retinas IGF1 activates PI-3 kinase (PI3K) but in neonatal retinas its action was identical to the action of an PI3K inhibitor. These data unveil a novel signaling cascade that co-ordinates and regulates rod differentiation through specific PKC isoforms in mammals.