Activated FGFR1 binds FLRT1,2,3

The three fibronectin-leucine-rich transmembrane (FLRT) proteins were identified as positive regulators of FGFR signaling that enhance FGFR-dependent RAS/MAPK pathway activation. All three FLRT proteins have been shown to interact with FGFR1 by co-immunoprecipitation and, at least in the case of FLRT3, the interaction is mediated by the FLRT fibronectin-like domain (Bottcher et al, 2004; Haines et al, 2006). Each FLRT gene has a distinct expression pattern and the strength of the protein-protein interaction with the FGF receptor varies, allowing for cell-type specific modulation of signaling activity (Haines et al, 2006). How the FLRT proteins act to enhance FGFR-dependent MAPK pathway activation is not clear, however FLRT1 has recently been shown to be phosphorylated in an FGFR1- and Src family kinase (SFK)-dependent manner (Wheldon et al, 2010).

三种富亮氨酸跨膜蛋白（FLRT）被确认为FGFR信号的正向调控因子，它们能够增强依赖于FGFR的RAS/MAPK通路激活。这三种FLRT蛋白均已被证明可以通过共免疫沉淀与FGFR1相互作用，且至少在FLRT3的情况下，这种相互作用是由FLRT的纤连蛋白样结构域（Bottcher等，2004；Haines等，2006）介导的。每个FLRT基因均具有独特的表达模式，且与FGF受体的蛋白质-蛋白质相互作用强度各异，从而允许对细胞特异性信号活动进行调节（Haines等，2006）。然而，FLRT蛋白如何作用于增强依赖于FGFR的MAPK通路激活尚不明确，但近期研究表明FLRT1在FGFR1和Src家族激酶（SFK）依赖性方式下发生磷酸化（Wheldon等，2010）。