Diestel Simone, Laurini Christine, Traub Otto, Schmitz Brigitte
Department of Biochemistry, Institute of Physiology, Biochemistry and Animal Health, Katzenburgweg 9a, 53115 Bonn, Germany.
Biochem Biophys Res Commun. 2004 Sep 10;322(1):186-96. doi: 10.1016/j.bbrc.2004.07.100.
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.
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。
