Dell'Albani P, Kahn M A, Cole R, Condorelli D F, Giuffrida-Stella A M, de Vellis J
Institute of Biochemistry, Faculty of Medicine, University of Catania, Sicily, Italy.
J Neurosci Res. 1998 Oct 15;54(2):191-205. doi: 10.1002/(SICI)1097-4547(19981015)54:2<191::AID-JNR7>3.0.CO;2-9.
Platelet-derived growth factor (PDGF) and ciliary neurotrophic factor (CNTF) have pleiotropic actions on many cell types. In the presence of these factors, oligodendroglia respond by enhanced survival when deprived of trophic factors or in the presence of the cytotoxic cytokine, tumor necrosis factor-alpha (TNF-alpha). To determine whether these two oligodendroglial survival factors converge in their signaling cascades, we examined their JAK/STAT pathways in enriched oligodendrocyte (OL) progenitors and in the progenitor OL cell line, central glia-4 (CG-4). Cytokine pathways such as JAK/STAT have been characterized extensively in hematopoietic cells; however, it is increasingly evident that the same cytokines that play a role in hematopoiesis also play a role during development and injury of the central nervous system. This is the first study that clearly defines the presence and activation of JAK/STAT proteins in OL progenitors and compares the signal transduction pathway of two well-known oligodendroglial survival factors. In this study, we report that PDGF- and CNTF-induced OL progenitors responded with a rapid tyrosine phosphorylation of JAK1, JAK2, STAT1alpha/beta, and STAT3. We feel that these identified JAK/STAT signaling molecules play a large role in the cellular response to these factors. Because both PDGF and CNTF enhance OL progenitor survival, these JAK/STATs may play a role in regulating this important cellular process.
血小板衍生生长因子（PDGF）和睫状神经营养因子（CNTF）对多种细胞类型具有多效性作用。在这些因子存在的情况下，少突胶质细胞在缺乏营养因子或存在细胞毒性细胞因子肿瘤坏死因子-α（TNF-α）时，会通过提高存活率做出反应。为了确定这两种少突胶质细胞存活因子在其信号级联反应中是否有共同之处，我们在富集少突胶质细胞（OL）祖细胞和祖细胞系中枢神经胶质-4（CG-4）中检测了它们的JAK/STAT信号通路。诸如JAK/STAT之类的细胞因子信号通路在造血细胞中已得到广泛研究；然而，越来越明显的是，在造血过程中起作用的相同细胞因子在中枢神经系统的发育和损伤过程中也发挥作用。这是第一项明确界定OL祖细胞中JAK/STAT蛋白的存在及激活情况，并比较两种著名的少突胶质细胞存活因子信号转导途径的研究。在本研究中，我们报告PDGF和CNTF诱导的OL祖细胞对JAK1、JAK2、STAT1α/β和STAT3出现快速酪氨酸磷酸化反应。我们认为这些已确定的JAK/STAT信号分子在细胞对这些因子的反应中起很大作用。由于PDGF和CNTF都能提高OL祖细胞的存活率，这些JAK/STAT可能在调节这一重要细胞过程中发挥作用。
