The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

成肌细胞的增殖和分化受成纤维细胞生长因子受体（FGFR）信号通路的调节。尽管已经广泛研究了FGFR信号转导级联的调节，但是在骨骼肌肌发生中特别起作用的抑制机制仍然不清楚。在这项研究中，我们确定LRTM1，FGFR信号通路的抑制性调节剂，负调节ERK的激活并促进成肌细胞的分化。LRTM1在成肌细胞分化和损伤后骨骼肌再生过程中动态表达。在小鼠成肌细胞C2C12细胞中，Lrtm1的敲除（KO）显着阻止成肌细胞的分化；这种作用与MyoD转录活性的降低和ERK激酶的过度活化有关。值得注意的是，进一步的研究表明LRTM1与p52Shc缔合并抑制p52Shc向FGFR1募集。综上所述，我们的发现确定了一种新型的FGFR1负调节剂，它在调节成肌细胞的分化中起着重要的作用。