Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration.
Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration.
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DOI：
10.1016/j.isci.2018.05.019
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发表时间：
2018-06-29
期刊：
影响因子：
5.8
通讯作者：
Igarashi M
中科院分区：
文献类型：
--
作者：
Kawasaki A;Okada M;Tamada A;Okuda S;Nozumi M;Ito Y;Kobayashi D;Yamasaki T;Yokoyama R;Shibata T;Nishina H;Yoshida Y;Fujii Y;Takeuchi K;Igarashi M
神经元生长锥对于神经生长和再生以及神经网络的形成和重排都是必不可少的。为了阐明依赖于磷酸化的信号通路，并建立有用的轴突生长和再生的分子标记，我们对哺乳动物生长锥体进行了磷酸蛋白质组学研究，鉴定了∼1,200蛋白的>；30,000个磷酸肽。由于JNK的激活，这些磷酸化位点高度依赖于MAPK，并高度依赖于Pro，这表明在哺乳动物的大脑中，经历了Pro指导的磷酸化的蛋白质介导了神经生长。生物信息学分析表明，磷蛋白在微管和皮质细胞骨架中丰富。最频繁的磷酸化位点是GAP-43(生长相关蛋白43-kDa)的S96，这是一种脊椎动物特有的蛋白质，参与轴突生长。这个先前未知的磷酸化位点依赖于JNK。S96在生长和再生轴突中被特异性地检测到，是JNK信号最常见的靶标，因此它是哺乳动物轴突生长和再生的一个有前途的新的分子标记。哺乳动物生长锥膜的磷蛋白质组学显示MAPK的激活JNK是生长锥中激活的MAPK，GAP-43中最常见的位置是GAP-43的pS96的磷酸化，在生长轴突中观察到pS96生化检测在周围神经再生轴突中检测到pS96神经科学；发育神经科学；生物信息学；蛋白质组学
Neuronal growth cones are essential for nerve growth and regeneration, as well as for the formation and rearrangement of the neural network. To elucidate phosphorylation-dependent signaling pathways and establish useful molecular markers for axon growth and regeneration, we performed a phosphoproteomics study of mammalian growth cones, which identified >30,000 phosphopeptides of ∼1,200 proteins. The phosphorylation sites were highly proline directed and primarily MAPK dependent, owing to the activation of JNK, suggesting that proteins that undergo proline-directed phosphorylation mediate nerve growth in the mammalian brain. Bioinformatics analysis revealed that phosphoproteins were enriched in microtubules and the cortical cytoskeleton. The most frequently phosphorylated site was S96 of GAP-43 (growth-associated protein 43-kDa), a vertebrate-specific protein involved in axon growth. This previously uncharacterized phosphorylation site was JNK dependent. S96 phosphorylation was specifically detected in growing and regenerating axons as the most frequent target of JNK signaling; thus it represents a promising new molecular marker for mammalian axonal growth and regeneration. Phosphoproteomics of mammalian growth cone membranes reveals activation of MAPK JNK is the activated MAPK in growth cones and phosphorylates S96 of GAP-43 pS96 of GAP-43, the most frequent site, is observed in growing axons pS96 is biochemically detected in the regenerating axons of the peripheral nerves Neuroscience; Developmental Neuroscience; Bioinformatics; Proteomics
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影响因子：
64.5
作者：
Huttlin EL;Jedrychowski MP;Elias JE;Goswami T;Rad R;Beausoleil SA;Villén J;Haas W;Sowa ME;Gygi SP
通讯作者：
Gygi SP
DOI：
10.1016/j.bbapap.2009.11.002
发表时间：
2010-03-01
影响因子：
3.2
作者：
Bogoyevitch, Marie A.;Ngoei, Kevin R. W.;Ng, Dominic C. H.
通讯作者：
Ng, Dominic C. H.
Kinasephos：用于识别蛋白激酶特异性磷酸化位点的Web工具。
影响因子：
14.9
作者：
Huang, HD;Lee, TY;Tzeng, SW;Horng, JT
通讯作者：
Horng, JT
影响因子：
3.7
作者：
Estrada-Bernal A;Sanford SD;Sosa LJ;Simon GC;Hansen KC;Pfenninger KH
通讯作者：
Pfenninger KH
影响因子：
7.2
作者：
Dent EW;Gupton SL;Gertler FB
通讯作者：
Gertler FB