氨酸诱导的FGF分子的寡合化是FGF受体二元化,激活和细胞增殖的原因
T Spivak-Kroizman1, M A Lemmon, I Dikic
1Department of Pharmacology, New York University Medical Center, New York 10016.
Cell
|December 16, 1994
概括
肝素对于纤维细胞生长因子 (FGF) 激活其受体 (FGFR) 是必不可少的. 氨酸会导致FGF聚合,使受体二分化和下游信号为细胞生长.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子信号传递是分子信号传递.
背景情况:
- 纤维细胞生长因子 (FGF) 与其受体 (FGFR) 结合对于细胞反应至关重要.
- 已知氨酸对于FGF介导的信号传递是必需的,但其确切的作用尚不清楚.
研究的目的:
- 阐明肝素促进FGF介导信号传递的机制.
- 为了研究肝素在FGF受体 (FGFR) 分解和激活中的作用.
主要方法:
- 异热定位热量计用于研究酸性FGF (aFGF) 和可溶性FGFR之间的相互作用.
- 在缺乏内源性肝硫酸盐的细胞系中进行了实验,以评估外源性肝的必要性.
- 一种合成氨酸模拟剂被用来探测氨酸多价值结合的作用.
主要成果:
- 酸性FGF (aFGF) 与可溶性FGFR细胞外域形成1:1复合体.
- 氨酸与多个aFGF分子结合,形成一个aFGF-氨酸复合体,能够结合多个FGFRs.
- 这种复杂的形成导致FGFR二分化,氨酸激酶激活,c-fos mRNA转录,以及缺陷细胞系中的细胞增殖.
- 一种单价氨酸模拟物抑制了FGFR二分化和下游信号传输.
结论:
- 氨酸诱导aFGF的寡合化,这促进了FGFR的二分化和随后的信号转导.
- 这项研究揭示了一种由肝素结合的生长因子介导的跨膜信号传递的新机制.
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