Protein kinase C showcases allosteric control: activation of LRRK1.
Protein kinase C showcases allosteric control: activation of LRRK1.
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DOI：
10.1042/bcj20220507
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发表时间：
2023-02-14
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多结构域蛋白激酶的变构调节提供了急性控制激酶活性的常见机制。蛋白激酶C作为多结构域蛋白质的范例，其活性通过结构域间构象变化精确地调节，所述结构域间构象变化在没有适当刺激的情况下保持酶关闭，但响应于第二信使结合而释放活性。蛋白激酶C信号的变构调节不仅针对自身进行了优化：Alessi及其同事发现，蛋白激酶C在其CORB GT3结构域上的位点磷酸化LRRK1（一种具有更多结构域的激酶），以变构方式激活LRRK1。
Allosteric regulation of multi-domain protein kinases provides a common mechanism to acutely control kinase activity. Protein kinase C serves as a paradigm for multi-domain proteins whose activity is exquisitely tuned by interdomain conformational changes that keep the enzyme off in the absence of appropriate stimuli, but unleash activity in response to second messenger binding. Allosteric regulation of protein kinase C signaling has been optimized not just for itself: Alessi and colleagues discover that protein kinase C phosphorylates LRRK1, a kinase with even more domains, at sites on its CORB GTPase domain to allosterically activate LRRK1.