p21 activated kinase 5 activates Raf-1 and targets it to mitochondria.
p21 activated kinase 5 activates Raf-1 and targets it to mitochondria.
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DOI：
10.1002/jcb.21809
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发表时间：
2008-09-01
影响因子：
4
通讯作者：
Frost, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Wu, Xiaochong;Carr, Heather S.;Dan, Ippeita;Ruvolo, Peter P.;Frost, Jeffrey A.
RAF-1是RAS介导的信号转导通路的重要效应者，也是ERK/MAPK信号通路的重要调节因子。RAF-1的激活部分由多个残基上的磷酸化控制，包括丝氨酸338处的专有磷酸化位点。此前，PAK1和酪蛋白激酶II被认为是丝氨酸338激酶。为了确定使该位点磷酸化的新的激酶，我们测试了第二组PAK(PAK4-6)控制丝氨酸338磷酸化的能力。我们观察到，尽管只有PAK1和PAK5显著刺激Raf-1激酶活性，但所有II组PAK都是有效的丝氨酸338激酶。我们还发现，PAK5在细胞内与Raf-1形成紧密的复合体，而不是A-Raf或B-Raf。重要的是，我们还证明了Raf-1与PAK5的关联针对线粒体的Raf-1亚群。这些数据表明，PAK5是Raf-1活性的有效调节者，可能控制线粒体上Raf-1依赖的信号转导。
Raf-1 is an important effector of Ras mediated signaling and is a critical regulator of the ERK/MAPK pathway. Raf-1 activation is controlled in part by phosphorylation on multiple residues, including an obligate phosphorylation site at serine 338. Previously PAK1 and casein kinase II have been implicated as serine 338 kinases. To identify novel kinases that phosphorylate this site, we tested the ability of group II PAKs (PAKs 4-6) to control serine 338 phosphorylation. We observed that all group II PAKs were efficient serine 338 kinases, although only PAK1 and PAK5 significantly stimulated Raf-1 kinase activity. We also showed that PAK5 forms a tight complex with Raf-1 in the cell, but not A-Raf or B-Raf. Importantly, we also demonstrated that the association of Raf-1 with PAK5 targets a subpopulation of Raf-1 to mitochondria. These data indicate that PAK5 is a potent regulator of Raf-1 activity and may control Raf-1 dependent signaling at the mitochondria.
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DOI：
10.1016/j.bbrc.2006.09.172
发表时间：
2006-12-15
影响因子：
3.1
作者：
Wu, Xiaochong;Frost, Jeffrey A.
通讯作者：
Frost, Jeffrey A.
影响因子：
4.8
作者：
Xiang, XQ;Zang, MW;Luo, ZJ
通讯作者：
Luo, ZJ
影响因子：
4.8
作者：
Jin, SH;Zhuo, Y;Field, J
通讯作者：
Field, J
影响因子：
9.2
作者：
Chaudhary, A;King, WG;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
64.8
作者：
King, AJ;Sun, HY;Marshall, MS
通讯作者：
Marshall, MS