Jaakkola P, Määttä A, Jalkanen M
Turku Centre for Biotechnology, University of Turku, Finland.
Oncogene. 1998 Sep 10;17(10):1279-86. doi: 10.1038/sj.onc.1202002.
The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in fibroblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In fibroblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in fibroblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factor-stimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in fibroblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in fibroblasts. Thirdly, EGF, which did not activate FiRE in fibroblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in fibroblasts. These data suggest mechanisms by which members of the EGF- and FGF-families can differentially stimulate transcription through AP-1 regulated elements in a cell type-specific manner.
硫酸乙酰肝素蛋白聚糖syndecan-1在发育和组织再生过程中，在角质形成细胞和成纤维细胞中均有表达。在此我们报告，在角质形成细胞中，syndecan-1基因受表皮生长因子（EGF）刺激，但不受成纤维细胞生长因子-2（FGF-2）刺激。在成纤维细胞中，它受FGF-2刺激，但不受EGF刺激。同样，最近在syndecan-1基因上发现的FGF诱导反应元件（FiRE），在成纤维细胞中受FGF-2刺激，在角质形成细胞中受EGF刺激，反之则不然。FiRE有两个激活蛋白-1（AP-1）的结合位点、一个FGF诱导核因子（FIN-1）的结合位点和一个上游刺激因子-1（USF-1）的结合位点。这些转录因子在生长因子刺激下的结合情况，以及它们对FiRE激活的需求，在两种细胞类型之间有所不同。首先，虽然两种细胞类型中激活FiRE都需要AP-1，但只有在成纤维细胞中，生长因子刺激会增加AP-1与FiRE的结合，而在角质形成细胞中则不会。其次，与成纤维细胞中FGF刺激激活FiRE不同，在角质形成细胞中，FiRE不结合FIN-1，EGF刺激激活FiRE也不需要FIN-1结合位点。第三，在成纤维细胞中不激活FiRE的EGF，在这些细胞中也不能激活FIN-1。最后，角质形成细胞中激活FiRE所必需的USF-1结合位点，在成纤维细胞中则不需要。这些数据表明了EGF家族和FGF家族成员能够以细胞类型特异性方式通过AP-1调节元件差异刺激转录的机制。
