S100A13 Is Involved in the Regulation of Fibroblast Growth Factor-1 and p40 Synaptotagmin-1 Release in Vitro

作者：Carla Mouta Carreira, Theresa M. LaVallee, Francesca Tarantini, Anthony Jackson, Julia Tait Lathrop, Brian Hampton, Wilson H. Burgess, Thomas Maciag · 发表于：Journal of Biological Chemistry · 年份：1998 · DOI：10.1074/jbc.273.35.22224 · 被引用次数：120 · 研究领域：S100 Proteins and Annexins、Neonatal Respiratory Health Research、Fibroblast Growth Factor Research

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.