Shimizu Akio, Takashima Yuji, Kurokawa-Seo Misuzu
Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan.
Biochem Biophys Res Commun. 2002 Jan 11;290(1):113-20. doi: 10.1006/bbrc.2001.6190.
We have previously cloned the alternatively spliced isoform of fibroblast growth factor receptor 3 (FGFR3DeltaAB) that lacks the acid box in the extracellular region. To understand the biological functions and signal transduction of these FGFR3 isoforms, we analyzed the effect of FGF1 in ATDC5 cells, chondroprogenitor cell lines overexpressing these isoforms. In response to FGF1, FGFR3 induced a marked cell-morphology change to a round shape, while FGFR3DeltaAB did not. Furthermore, FGFR3 induced complete growth arrest, whereas FGFR3DeltaAB induced only moderate growth inhibition. Both receptors induced the expression of the CDK inhibitor p21(CIP1). However, only FGFR3 induced STAT1 phosphorylation that mediates the transcriptional induction of p21(CIP1), although both FGFR3 isoforms could induce a strong activation of mitogen-activated protein (MAP) kinases. Taken together, the different biological responses mediated by FGFR3 and FGFR3DeltaAB appear to be due to a difference in their ability to utilize STAT1 pathway and signals involved in cell rounding.
我们之前克隆了成纤维细胞生长因子受体3（FGFR3DeltaAB）的可变剪接异构体，该异构体在细胞外区域缺乏酸性盒。为了了解这些FGFR3异构体的生物学功能和信号转导，我们分析了FGF1对ATDC5细胞（过表达这些异构体的软骨祖细胞系）的影响。响应FGF1时，FGFR3诱导细胞形态显著改变为圆形，而FGFR3DeltaAB则无此现象。此外，FGFR3诱导完全生长停滞，而FGFR3DeltaAB仅诱导中度生长抑制。两种受体均诱导细胞周期蛋白依赖性激酶抑制剂p21（CIP1）的表达。然而，只有FGFR3诱导介导p21（CIP1）转录诱导的STAT1磷酸化，尽管两种FGFR3异构体均可诱导丝裂原活化蛋白（MAP）激酶的强烈激活。综上所述，FGFR3和FGFR3DeltaAB介导的不同生物学反应似乎是由于它们利用STAT1途径的能力以及与细胞变圆相关信号的差异所致。
