The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit.
The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit.
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DOI：
10.1083/jcb.201404095
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发表时间：
2015-01-19
期刊：
影响因子：
--
通讯作者：
Barber DL
中科院分区：
文献类型：
--
作者：
LeClaire LL;Rana M;Baumgartner M;Barber DL
激酶NIK对Arp2的磷酸化增加了Arp2/3复合物的肌动蛋白成核活性，这是响应EGF的质膜突出所必需的。Arp2/3复合体的成核活性促进了分支肌动蛋白丝的组装，从而驱动迁移细胞中的质膜突出。Arp2/3复合物与WASP和WAVE家族的成核促进因子结合，先前被认为足以增加成核活性。然而，Arp2亚基的磷酸化最近被证明是Arp2/3复合物活性的必要条件。我们发现，在乳腺癌细胞中，缺乏磷酸化的突变Arp2与内源性亚基组装，并主要抑制肌动蛋白丝组装和膜突出。我们还报道了nck相互作用激酶（NIK），一种MAP4K4，结合并直接磷酸化Arp2亚基，从而增加Arp2/3复合物的成核活性。在细胞中，NIK激酶活性是增加Arp2磷酸化和响应表皮生长因子的质膜突出所必需的。NIK是第一个磷酸化并增加Arp2/3复合物活性的激酶，我们的研究结果表明它整合了生长因子对肌动蛋白丝动力学的调节。
Arp2 phosphorylation by the kinase NIK increases the actin-nucleating activity of the Arp2/3 complex and is necessary for plasma membrane protrusion in response to EGF. The nucleating activity of the Arp2/3 complex promotes the assembly of branched actin filaments that drive plasma membrane protrusion in migrating cells. Arp2/3 complex binding to nucleation-promoting factors of the WASP and WAVE families was previously thought to be sufficient to increase nucleating activity. However, phosphorylation of the Arp2 subunit was recently shown to be necessary for Arp2/3 complex activity. We show in mammary carcinoma cells that mutant Arp2 lacking phosphorylation assembled with endogenous subunits and dominantly suppressed actin filament assembly and membrane protrusion. We also report that Nck-interacting kinase (NIK), a MAP4K4, binds and directly phosphorylates the Arp2 subunit, which increases the nucleating activity of the Arp2/3 complex. In cells, NIK kinase activity was necessary for increased Arp2 phosphorylation and plasma membrane protrusion in response to epidermal growth factor. NIK is the first kinase shown to phosphorylate and increase the activity of the Arp2/3 complex, and our findings suggest that it integrates growth factor regulation of actin filament dynamics.
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DOI：
10.1083/jcb.201103045
发表时间：
2011-11-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Magalhaes MA;Larson DR;Mader CC;Bravo-Cordero JJ;Gil-Henn H;Oser M;Chen X;Koleske AJ;Condeelis J
通讯作者：
Condeelis J
影响因子：
9.2
作者：
Poinat, P;De Arcangelis, A;Labouesse, EG
通讯作者：
Labouesse, EG
影响因子：
48
作者：
Riedl, Julia;Crevenna, Alvaro H.;Wedlich-Soldner, Roland
通讯作者：
Wedlich-Soldner, Roland
影响因子：
3.7
作者：
El-Sibai, Mirvat;Pertz, Olivier;Backer, Jonathan M.
通讯作者：
Backer, Jonathan M.
影响因子：
4.8
作者：
Kelly, AE;Kranitz, H;Mullins, RD
通讯作者：
Mullins, RD