Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Blegdamsvej 3C, Building 24.2, Copenhagen N, DK-2200, Denmark.
J Neurosci Res. 2010 Jul;88(9):1882-9. doi: 10.1002/jnr.22374.
Activation of fibroblast growth factor (FGF) receptors (FGFRs) both by FGFs and by the neural cell adhesion molecule (NCAM) is crucial in the development and function of the nervous system. We found that FGFR substrate 2alpha (FRS2alpha), Src homologous and collagen A (ShcA), and phospholipase-Cgamma (PLCgamma) were all required for neurite outgrowth from cerebellar granule neurons (CGNs) induced by FGF1 and FGL (an NCAM-derived peptide agonist of FGFR1). Like FGF1, FGL induced tyrosine phosphorylation of FGFR1, FRS2alpha, ShcA, and PLCgamma in a time- and dose-dependent manner. However, the activation of FRS2alpha by FGL was significantly lower than the activation by FGF1, indicating a differential signaling profile induced by NCAM compared with the cognate growth factor.
成纤维细胞生长因子 (FGF) 受体 (FGFR) 的激活，无论是由 FGF 还是由神经细胞黏附分子 (NCAM) 激活，在神经系统的发育和功能中都至关重要。我们发现，成纤维细胞生长因子底物 2α（FRS2alpha）、Src 同源和胶原 A（ShcA）以及磷脂酶-Cγ（PLCγ），对于小脑颗粒神经元（CGNs）在 FGF1 和 FGL（一种 FGFR1 的 NCAM 衍生肽激动剂）诱导下的突起生长都是必需的。与 FGF1 一样，FGL 以时间和剂量依赖的方式诱导 FGFR1、FRS2alpha、ShcA 和 PLCγ 的酪氨酸磷酸化。然而，FGL 对 FRS2alpha 的激活明显低于 FGF1 的激活，表明与同源生长因子相比，NCAM 诱导的信号转导谱存在差异。
