Meuillet E, Crémel G, Hicks D, Dreyfus H
INSERM U. 338, Centre de Neurochimie, Strasbourg, France.
J Lipid Mediat Cell Signal. 1996 Sep;14(1-3):277-88. doi: 10.1016/0929-7855(96)00536-6.
Gangliosides have long been implicated in cell growth regulation and play an important role as modulators in protein phosphorylation. In order to better understand how glycosphingolipids and growth factors interact, we examined the modulation of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) effects on retinal Müller glial cells (RMG), following modification of their GG composition. Treatment of MG cells with GG (GM1, GT1b) and asialoGM1 resulted in modifications of several aspects of cellular responses to EGF- and FGF-receptor (R) activation: mitogenesis, cell migration, tyrosine phosphorylation of the EGF-R and FGF-R and even their cellular substrates were particularly influenced by GG. Indeed GG caused modifications of EGF-R and FGF-R autophosphorylation kinetics. GG long term effects (mitogenesis and migration) correlate with short term effects (tyrosine phosphorylation) and differences in receptor tyrosine kinase signalling could explain the specificity in growth factor responses.
神经节苷脂长期以来一直被认为与细胞生长调节有关,并在蛋白质磷酸化过程中作为调节剂发挥重要作用。为了更好地理解糖鞘脂与生长因子如何相互作用,我们在改变视网膜穆勒神经胶质细胞(RMG)的神经节苷脂(GG)组成后,研究了表皮生长因子(EGF)和碱性成纤维细胞生长因子(bFGF)对其作用的调节。用GG(GM1、GT1b)和去唾液酸GM1处理穆勒神经胶质细胞,导致细胞对EGF受体(R)和FGF受体(R)激活的多种反应发生改变:有丝分裂、细胞迁移、EGF-R和FGF-R的酪氨酸磷酸化,甚至它们的细胞底物都受到GG的特别影响。实际上,GG导致了EGF-R和FGF-R自身磷酸化动力学的改变。GG的长期作用(有丝分裂和迁移)与短期作用(酪氨酸磷酸化)相关,受体酪氨酸激酶信号传导的差异可以解释生长因子反应的特异性。