Immunology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA.
Antioxid Redox Signal. 2011 Mar 1;14(5):757-66. doi: 10.1089/ars.2010.3773. Epub 2011 Jan 4.
Protein kinase C (PKC) is activated by lipid second messengers or redox action, raising the question whether these activation modes involve the same or alternate mechanisms. Here we show that both lipid activators and oxidation target the zinc-finger domains of PKC, suggesting a unifying activation mechanism. We found that lipid agonist-binding or redox action leads to zinc release and disassembly of zinc fingers, thus triggering large-scale unfolding that underlies conversion to the active enzyme. These results suggest that PKC zinc fingers, originally considered purely structural devices, are in fact redox-sensitive flexible hinges, whose conformation is controlled both by redox conditions and lipid agonists.
蛋白激酶 C（PKC）被脂类第二信使或氧化还原作用激活，这就提出了一个问题，即这些激活方式是否涉及相同或不同的机制。在这里，我们表明，脂类激活剂和氧化作用都靶向 PKC 的锌指结构域，这表明存在一个统一的激活机制。我们发现，脂类激动剂结合或氧化还原作用导致锌的释放和锌指的解体，从而引发大规模的展开，这是向活性酶转化的基础。这些结果表明，PKC 的锌指结构域，最初被认为是纯粹的结构装置，实际上是氧化还原敏感的柔性铰链，其构象不仅受氧化还原条件的控制，还受脂类激动剂的控制。
