Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes.
Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes.
复制标题
少突胶质细胞中成纤维细胞生长因子受体 2 的磷酸化和脂筏关联。
作者：
Bryant, M. R.;Marta, C. B.;Kim, F. S.;Bansal, R.
成纤维细胞生长因子(FGFs)及其受体(FGFRs)启动多种细胞反应，有助于调节少突胶质细胞(OL)的功能。为了了解FGFRs诱导这些细胞反应的机制，我们研究了信号转导蛋白的磷酸化和胆固醇-鞘糖脂富含的“脂筏”微域在分化的OL中的作用。令人惊讶的是，我们发现在OL中最丰富的酪氨酸磷酸化蛋白是FGFR2的120kd亚型，并且即使在没有FGF2的情况下它也被磷酸化，这表明该受体具有潜在的配体无关的功能。此外，FGFR2，而不是FGFR1，与OL和髓鞘中的脂筏微域相关(但在星形胶质细胞中不相关)。这为FGFR与TX-100不溶性脂筏组分的关联提供了第一个证据。FGFR2使OLS中的关键下游靶FRS2磷酸化。RAFT断裂导致脂筏上磷酸化FRS2的丢失，伴随Akt的丢失，但不包括MEK或Erk的磷酸化。这表明FGFR2-FRS2信号在脂筏中通过PI3-Kinase/Akt途径而不是Ras/MEK/Erk途径发挥作用，强调了细胞膜内微环境的重要性。一种新的52 kd的FGFR2亚型也存在于OL和髓鞘的脂筏中，但不存在于星形胶质细胞中，该亚型缺乏细胞外配体结合区。这些结果表明，OLS和髓鞘中的FGFR2具有受体类型和OLS特异性的独特特征，并提供了一种新的机制来诱导不同的细胞反应，介导成纤维细胞生长因子依赖和非依赖的功能。
Fibroblast growth factors (FGFs) and their receptors (FGFRs) initiate diverse cellular responses that contribute to the regulation of oligodendrocyte (OL) function. In order to understand the mechanisms by which FGFRs elicit these cellular responses, we investigated the phosphorylation of signal transduction proteins and the role of cholesterol-glycosphingolipid-enriched “lipid raft” microdomains in differentiated OLs. Surprisingly, we found that the most abundant tyrosine-phosphorylated protein in OLs was the 120-kd isoform of FGFR2 and that it was phosphorylated even in the absence of FGF2, suggesting a potential ligand-independent function for this receptor. Furthermore, FGFR2, but not FGFR1, was associated with lipid raft microdomains in OLs and myelin (but not in astrocytes). This provides the first evidence for the association of FGFR with TX-100-insoluble lipid raft fractions. FGFR2 phosphorylated the key downstream target, FRS2 in OLs. Raft disruption resulted in loss of phosphorylated FRS2 from lipid rafts, coupled with the loss of Akt but not of Mek or Erk phosphorylation. This suggests that FGFR2-FRS2 signaling in lipid rafts operates via the PI3-Kinase/Akt pathway rather than the Ras/Mek/Erk pathway, emphasizing the importance of microenvironments within the cell membrane. Also present in lipid rafts in OLs and myelin, but not in astrocytes, was a novel 52-kd isoform of FGFR2 that lacked the extracellular ligand-binding region. These results demonstrate that FGFR2 in OLs and myelin possess unique characteristics that are specific both to receptor type and to OLs and provide a novel mechanism to elicit distinct cellular responses that mediate both FGF-dependent and -independent functions.
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影响因子：
7.8
作者：
HANNEKEN, A;MAHER, PA;BAIRD, A
通讯作者：
BAIRD, A
影响因子：
3.5
作者：
Christensen, Claus;Lauridsen, Jes B.;Kiselyov, Vladislav V.
通讯作者：
Kiselyov, Vladislav V.
DOI：
10.3109/08977199109000276
发表时间：
1991-01-01
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Kiefer, M C;Baird, A;Barr, P J
通讯作者：
Barr, P J
影响因子：
5.3
作者：
Fortin, D;Rom, E;Bansal, R
通讯作者：
Bansal, R
影响因子：
9.2
作者：
Baron, W;Decker, L;ffrench-Constant, C
通讯作者：
ffrench-Constant, C