Yim S H, Hammer J A, Quarles R H
Myelin and Brain Development Section, Laboratory of Molecular and Cellular Neurobiology, NINDS, NIH, Bethesda, Maryland 20892, USA.
J Neurochem. 2001 Mar;76(6):1925-34. doi: 10.1046/j.1471-4159.2001.00199.x.
Treatment of cultured rat oligodendroglial progenitors with either platelet-derived growth factor (PDGF) or fibroblast growth factor-2 (FGF-2) activated extracellular signal regulated kinase 2 (ERK2). Activation was transient in response to PDGF, whereas it was greater and more prolonged in response to FGF-2. ERK2 activation by PDGF was preceded by a very rapid, robust and transient tyrosine phosphorylation of the PDGF receptor. Although there was consistently more activation of ERK2 in response to FGF-2 than to PDGF, immunostaining of FGF receptors 1 (FGFR1) and 2 (FGFR2) and their tyrosine phosphorylation in progenitors was very weak, and both receptors were up-regulated during differentiation to oligodendrocytes. Tyrosine phosphorylation of the FGF receptors was maximal from 15 to 60 min of treatment and was sustained for many hours. Binding of radioiodinated FGF-2 to FGFR1 was predominant in progenitors, whereas binding to FGFR2 was predominant in oligodendrocytes. ERK2 activation by PDGF was more sensitive to inhibition of tyrosine kinases, whereas ERK2 activation by FGF-2 was relatively more sensitive to inhibitors of protein kinase C. These differences in signal transduction pathways probably contribute to the different cellular responses of oligodendroglial lineage cells to PDGF and FGF-2, respectively.
用血小板衍生生长因子（PDGF）或成纤维细胞生长因子-2（FGF-2）处理培养的大鼠少突胶质前体细胞会激活细胞外信号调节激酶2（ERK2）。对PDGF的反应中激活是短暂的，而对FGF-2的反应中激活程度更大且持续时间更长。PDGF激活ERK2之前，PDGF受体有非常快速、强烈且短暂的酪氨酸磷酸化。尽管对FGF-2的反应中ERK2的激活始终比对PDGF的反应更多，但前体细胞中FGF受体1（FGFR1）和2（FGFR2）的免疫染色及其酪氨酸磷酸化非常弱，并且在向少突胶质细胞分化过程中这两种受体均上调。FGF受体的酪氨酸磷酸化在处理15至60分钟时达到最大值，并持续数小时。放射性碘化FGF-2与FGFR1的结合在前体细胞中占主导，而与FGFR2的结合在少突胶质细胞中占主导。PDGF激活ERK2对酪氨酸激酶抑制更敏感，而FGF-2激活ERK2对蛋白激酶C抑制剂相对更敏感。信号转导途径的这些差异可能分别导致少突胶质谱系细胞对PDGF和FGF-2的不同细胞反应。
