Mouta Carreira C, LaVallee T M, Tarantini F, Jackson A, Lathrop J T, Hampton B, Burgess W H, Maciag T
Center for Molecular Medicine, Maine Medical Center Research Institute, South Portland, Maine 04106, USA.
J Biol Chem. 1998 Aug 28;273(35):22224-31. doi: 10.1074/jbc.273.35.22224.
We have previously characterized the release of the signal peptide sequence-less fibroblast growth factor (FGF) prototype, FGF-1, in vitro as a stress-induced pathway in which FGF-1 is released as a latent homodimer with the p40 extravesicular domain of p65 synaptotagmin (Syn)-1. To determine the biologic relevance of the FGF-1 release pathway in vivo, we sought to resolve and characterize from ovine brain a purified fraction that contained both FGF-1 and p40 Syn-1 and report that the brain-derived FGF-1:p40 Syn-1 aggregate is associated with the calcium-binding protein, S100A13. Since S100A13 binds the anti-inflammatory compound amlexanox and FGF-1 is involved in inflammation, we examined the effects of amlexanox on the release of FGF-1 and p40 Syn-1 in response to stress in vitro. We report that while amlexanox was able to repress the heat shock-induced release of FGF-1 and p40 Syn-1 in a concentration-dependent manner, it had no effect on the constitutive release of p40 Syn-1 from p40 Syn-1 NIH 3T3 cell transfectants. These data suggest the following: (i) FGF-1 is associated with Syn-1 and S100A13 in vivo; (ii) S100A13 may be involved in the regulation of FGF-1 and p40 Syn-1 release in response to temperature stress in vitro; and (iii) the FGF-1 release pathway may be accessible to pharmacologic regulation.
我们之前已将无信号肽序列的成纤维细胞生长因子（FGF）原型FGF-1的体外释放，描述为一种应激诱导途径，即FGF-1作为一种潜在的同二聚体与p65突触结合蛋白（Syn）-1的p40细胞外结构域一起释放。为了确定FGF-1释放途径在体内的生物学相关性，我们试图从绵羊大脑中分离并鉴定出一个同时含有FGF-1和p40 Syn-1的纯化组分，并报告源自大脑的FGF-1:p40 Syn-1聚集体与钙结合蛋白S100A13相关。由于S100A13结合抗炎化合物氨来呫诺且FGF-1参与炎症反应，我们研究了氨来呫诺对体外应激反应中FGF-1和p40 Syn-1释放的影响。我们报告称，虽然氨来呫诺能够以浓度依赖的方式抑制热休克诱导的FGF-1和p40 Syn-1释放，但它对p40 Syn-1 NIH 3T3细胞转染子中p40 Syn-1的组成型释放没有影响。这些数据表明：（i）FGF-1在体内与Syn-1和S100A13相关；（ii）S100A13可能参与体外温度应激反应中FGF-1和p40 Syn-1释放的调节；（iii）FGF-1释放途径可能受药物调节。
