Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4.
Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4.
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DOI：
10.1042/bj20130281
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发表时间：
2013-10-15
期刊：
影响因子：
--
通讯作者：
Storz P
中科院分区：
文献类型：
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作者：
Bastea LI;Döppler H;Pearce SE;Durand N;Spratley SJ;Storz P
p21 激活激酶 (PAK) 是 RhoGTPases 的效应器。 PAK4 通过激活 Lin-11/Isl-1/Mec-3 激酶 (LIMK) 来调节迁移细胞前缘的肌动蛋白丝切蛋白 (cofilin)。 PAK4 活性由自抑制结构域调节，该结构域在 RhoGTPase 结合以及激酶结构域激活环中丝氨酸 474 处磷酸化时释放。我们在这里通过证明丝氨酸残基 99 的磷酸化是其靶向前缘所必需的，为 PAK4 调节增加了另一个层次的复杂性。这种磷酸化是由蛋白激酶 D1 (PKD1) 介导的。 PAK4 在 S99 处的磷酸化还介导与 14-3-3 蛋白的结合，并且是形成调节丝切蛋白活性和定向细胞迁移的 PAK4/LIMK/PKD1 复合物所必需的。
p21-activated kinases (PAKs) are effectors of RhoGTPases. PAK4 contributes to regulation of cofilin at the leading edge of migrating cells through activation of Lin-11/Isl-1/Mec-3 kinase (LIMK). PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at serine 474 in the activation loop of the kinase domain. We here add another level of complexity to PAK4 regulation by showing that phosphorylation at serine residue 99 is required for its targeting to the leading edge. This phosphorylation is mediated by protein kinase D1 (PKD1). Phosphorylation of PAK4 at S99 also mediates binding to 14-3-3 protein, and is required for the formation of a PAK4/LIMK/PKD1 complex that regulates cofilin activity and directed cell migration.