Autoregulation of the Raf-1 serine/threonine kinase
Autoregulation of the Raf-1 serine/threonine kinase
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DOI：
10.1073/pnas.95.16.9214
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Morrison, DK
中科院分区：
文献类型：
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作者：
Cutler, RE;Stephens, RM;Morrison, DK
Raf-1丝氨酸/苏氨酸激酶是参与许多生长和发育信号传递的关键蛋白。在这篇报道中，我们发现Raf-1的N端非催化调节区介导的自体抑制是调节Raf-1功能的重要机制，调节区的抑制至少部分是通过与富含半胱氨酸的结构域的结合作用发生的。破坏这种自身抑制的事件，例如富含半胱氨酸的结构域的突变或模拟活化磷酸化事件（Y340 D）的突变，减轻调节区的抑制并增加Raf-1活性。基于丝氨酸/苏氨酸激酶蛋白激酶C、Byr 2和Raf-1的自动调节之间惊人的相似性，我们提出解除质膜上的自动抑制和激活是一种进化上保守的激酶调节机制。
The Raf-1 serine/threonine kinase is a key protein involved in the transmission of many growth and developmental signals. Im this report, we sinew that antoinhibition mediated by the noncatalytic, N-terminal regulatory region of Raf-1 is an important mechanism regulating Raf-1 function, The inhibition of the regulatory region occurs, at lease in part, through binding interactions involving the cysteine-rich domain. Events that disrupt this autoinhibition, such as mutation of the cysteine-rich domain or a mutation mimicking an activating phosphorylation event (Y340D), alleviate the repression of the regulatory region and increase Raf-1 activity. Based on the striking similarites ibt tween the autoregulation of the serine/threonine kinases protein kinase C, Byr2, and Raf-1, we propose that relief of autorepression and activation at the plasma membrane is an evolutionarily conserved mechanism of kinase regulation.