Foletti A, Vuadens F, Beermann F
ISREC (Swiss Institute for Experimental Cancer Research), NCCR Molecular Oncology, Chemin des Boveresses 155, 1066 Epalinges s/Lausanne, Switzerland.
Cell Mol Life Sci. 2003 Oct;60(10):2254-65. doi: 10.1007/s00018-003-3258-6.
In vertebrates, different isoforms of fibroblast growth factor 2 (FGF2) exist, which differ by their N-terminal extension. They show different localization and expression levels and exert distinct biological effects. Nevertheless, genetic inactivation of all FGF2 isoforms in the mouse results in only mild phenotypes. Here, we analyzed mouse FGF2, and show that, as in the human, mouse FGF2 contains CTG-initiated high molecular-weight (HMW) isoforms, which contain a nuclear localization signal, and which mediate localization of this isoform to the nucleus. Using green fluorescent protein-FGF2 fusions, we furthermore observed, that C-terminal deletions disable nuclear localization of the short low-molecular-weight (LMW) 18-kDa isoform. This loss of specific localization is accompanied by a loss in heparin binding. We therefore suggest that, first, localization of mouse FGF2 is comparable to that in other vertebrates and, second, FGF2 contains at least two sequences important for nuclear localization, a nuclear localization sequence at the N terminus which is only contained in the HMW isoform, and another sequence at the C terminus, which is only required for localization of the LMW 18-kDa isoform.
在脊椎动物中，存在成纤维细胞生长因子2（FGF2）的不同同工型，它们在N端延伸部分有所不同。它们表现出不同的定位和表达水平，并发挥不同的生物学效应。然而，小鼠中所有FGF2同工型的基因失活仅导致轻微的表型。在此，我们分析了小鼠FGF2，并表明，与人类一样，小鼠FGF2包含由CTG起始的高分子量（HMW）同工型，其含有核定位信号，并介导该同工型定位于细胞核。使用绿色荧光蛋白-FGF2融合体，我们还观察到，C端缺失会使短的低分子量（LMW）18 kDa同工型的核定位丧失。这种特异性定位的丧失伴随着肝素结合能力的丧失。因此，我们认为，首先，小鼠FGF2的定位与其他脊椎动物中的定位相当，其次，FGF2包含至少两个对核定位重要的序列，一个位于N端的核定位序列，仅存在于HMW同工型中，另一个位于C端的序列，仅为LMW 18 kDa同工型的定位所必需。
