PDGF and FGF-2 signaling in oligodendrocyte progenitor cells: Regulation of proliferation and differentiation by multiple intracellular signaling pathways
PDGF and FGF-2 signaling in oligodendrocyte progenitor cells: Regulation of proliferation and differentiation by multiple intracellular signaling pathways
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DOI：
10.1006/mcne.1999.0827
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发表时间：
2000-03-01
影响因子：
3.5
通讯作者：
de Vries, H
中科院分区：
文献类型：
--
作者：
Baron, W;Metz, B;de Vries, H
在这篇文章中，我们讨论了血小板衍生生长因子(PDGF)和碱性成纤维细胞生长因子(FGF-2)与少突胶质细胞前体细胞内信号分子的连接。研究表明，这两种生长因子激活的下游靶点与蛋白激酶C(PKC)的激活类似。然而，抑制PKC不能拮抗PDGF或FGF-5对少突胶质细胞终末分化的抑制作用和对其增殖的诱导作用。相反，p42/p44丝裂原活化蛋白激酶(MAPK)、p38MAPK和pp70 S6激酶被发现是PDGF和FGF-2有丝分裂活性所必需的。矛盾的是，在对照细胞中，这些激酶也是少突胶质细胞分化的开始所必需的。此外，cAMP依赖的激酶A(PKA)的激活抑制了少突胶质前体细胞对成纤维细胞生长因子-P的促有丝分裂反应。综上所述，控制少突胶质细胞谱系发展的分子机制至少由两条信号通路操纵，这两条信号通路干扰了少突胶质细胞前体细胞的增殖和/或分化。
In this paper we address the linking of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (FGF-2) to intracellular signaling molecules in oligodendrocyte progenitors. It is demonstrated that both growth factors activate downstream targets similar to those shown for protein kinase C (PKC) activation. Yet, neither the arrest of terminal oligodendrocyte differentiation nor the proliferation induced by PDGF or FGF-5 can be antagonized by inhibition of PKC. Rather, p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK, and pp70 S6 kinase were found to be necessary for the mitogenic activity of PDGF and FGF-2. Paradoxically, these kinases were also necessary for the onset of oligodendrocyte differentiation in control cells. In addition, cAMP-dependent kinase A (PKA) activation inhibited the mitogenic response of oligodendrocyte progenitors to FGF-P. Taken together, the molecular mechanism that controls oligodendrocyte lineage progression is operated by at least two signal pathways, which interfere either with proliferation and/or differentiation of oligodendrocyte progenitors.