Localization of platelet-derived growth factor-stimulated phosphorylation cascade to caveolae
Localization of platelet-derived growth factor-stimulated phosphorylation cascade to caveolae
复制标题
DOI：
10.1074/jbc.271.17.10299
复制
发表时间：
1996-04-26
影响因子：
4.8
通讯作者：
Anderson, RGW
中科院分区：
文献类型：
--
作者：
Liu, PS;Ying, YS;Anderson, RGW
以前，我们表明，白细胞介素1 β刺激神经鞘磷脂的神经酰胺在正常人成纤维细胞的小窝部分的转换。神经酰胺反过来又阻断了血小板衍生生长因子（PDGF）刺激的DNA合成。我们现在提出的证据表明，PDGF受体启动信号转导从小窝。细胞分级分离和免疫细胞化学显示小窝是PDGF受体在细胞表面的主要位置。当PDGF与其受体结合时，多个小窝蛋白获得磷酸化酪氨酸，但该激素似乎对非小窝膜蛋白的酪氨酸磷酸化几乎没有影响。五种已知与磷酸化受体相互作用的蛋白质被发现高度富集在小窝膜中。PDGF导致这些蛋白质中的三种的浓度在小窝部分中显著增加。最后，PDGF刺激了190 kDa磷蛋白与小窝标记蛋白小窝蛋白的结合。因此，神经酰胺可能直接调节小窝中的血小板衍化生长因子受体功能。
Previously we showed that interleukin 1 beta stimulates the conversion of sphingomyelin to ceramide in the caveolae fraction of normal human fibroblasts. The ceramide, in turn, blocked platelet-derived growth factor (PDGF) stimulated DNA synthesis. We now present evidence that the PDGF receptor initiates signal transduction from caveolae. Cell fractionation and immunocytochemistry show caveolae to be the principal location of PDGF receptors at the cell surface. Multiple caveolae proteins acquire phosphotyrosine when PDGF binds to its receptor, but the hormone appears to have little effect on the tyrosine phosphorylation of non-caveolae membrane proteins. Five proteins known to interact with the phosphorylated receptor were found to be highly enriched in caveolae membrane. PDGF caused the concentration of three of these proteins to significantly increase in the caveolae fraction. Finally, PDGF stimulated the association of a 190-kDa phosphoprotein with the caveolae marker protein, caveolin. Therefore, ceramide may modulate PDGF receptor function directly in caveolae.