NCAM180的酪氨酸734干扰了与神经突生长相关的成纤维细胞生长因子受体依赖性信号传导。

Tyrosine 734 of NCAM180 interferes with FGF receptor-dependent signaling implicated in neurite growth.

作者信息

Diestel Simone, Laurini Christine, Traub Otto, Schmitz Brigitte

机构信息

Department of Biochemistry, Institute of Physiology, Biochemistry and Animal Health, Katzenburgweg 9a, 53115 Bonn, Germany.

出版信息

Biochem Biophys Res Commun. 2004 Sep 10;322(1):186-96. doi: 10.1016/j.bbrc.2004.07.100.

DOI:10.1016/j.bbrc.2004.07.100

PMID:15313190

Abstract

The cytoplasmic domain of the neural cell adhesion molecule (NCAM) contains multiple phosphorylation sites. We report here that in addition to serine and threonine residues a tyrosine of the NCAM180 isoform is phosphorylated as shown by phosphoamino acid analysis. Exchange of the only cytoplasmic tyrosine at position 734 of human NCAM180 (NCAM180-Y734F) to phenylalanine resulted in increased neurite outgrowth of NCAM180-Y734F transfected B35 neuroblastoma cells compared to NCAM180-wt transfectants on poly-L-lysine as substrate. As demonstrated by inhibitor studies the increased neurite outgrowth was due to higher FGF receptor 1 and ERK1 activity in NCAM180-Y734F cells, indicating that tyrosine residue 734 plays a role in signal transduction mediated by the FGF receptor. On an NCAM expressing monolayer of COS-7 cells the Y734F mutation also influences FGF receptor 1 dependent neurite outgrowth, but under these conditions additional mechanisms seem to be responsible for the increased neurite length observed for NCAM180-Y734F transfected cells.

摘要

神经细胞黏附分子（NCAM）的胞质结构域包含多个磷酸化位点。我们在此报告，通过磷酸氨基酸分析表明，除了丝氨酸和苏氨酸残基外，NCAM180亚型的一个酪氨酸也被磷酸化。将人NCAM180（NCAM180 - Y734F）第734位唯一的胞质酪氨酸替换为苯丙氨酸，结果显示，与在聚-L-赖氨酸作为底物上的NCAM180野生型转染细胞相比，NCAM180 - Y734F转染的B35神经母细胞瘤细胞的神经突生长增加。抑制剂研究表明，神经突生长增加是由于NCAM180 - Y734F细胞中较高的成纤维细胞生长因子受体1（FGF受体1）和细胞外信号调节激酶1（ERK1）活性，这表明第734位酪氨酸残基在FGF受体介导的信号转导中起作用。在表达NCAM的COS - 7细胞单层上，Y734F突变也影响FGF受体1依赖性神经突生长，但在这些条件下，其他机制似乎对NCAM180 - Y734F转染细胞中观察到的神经突长度增加负责。