ノズミ　モトヒロ   野住　素広    所属   新潟薬科大学  医療技術学部 臨床検査学科    職種   教授
言語種別	英語
発行・発表の年月	2018/06/29
形態種別	論文 - 研究論文（学術雑誌）
査読	査読あり
標題	Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration.
執筆形態	その他 - 指定なし
掲載誌名	iScience
掲載区分	国外
巻・号・頁	4,pp.190-203
著者・共著者	Asami Kawasaki,Masayasu Okada,Atsushi Tamada,Shujiro Okuda,Motohiro Nozumi,Yasuyuki Ito,Daiki Kobayashi,Tokiwa Yamasaki,Ryo Yokoyama,Takeshi Shibata,Hiroshi Nishina,Yutaka Yoshida,Yukihiko Fujii,Kosei Takeuchi,Michihiro Igarashi
概要	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.
DOI	10.1016/j.isci.2018.05.019
PMID	30240740