Szewczyk Nathaniel J, Jacobson Lewis A
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
EMBO J. 2003 Oct 1;22(19):5058-67. doi: 10.1093/emboj/cdg472.
Signaling by fibroblast growth factors (FGFs) and their receptors has been previously implicated in control of cell proliferation, differentiation and migration. Here we report a novel role for signaling by the EGL-15 FGFR of Caenorhabditis elegans in controlling protein degradation in differentiated muscle. Activation of EGL-15, by means of a reduction of function mutation (clr-1) affecting an inhibitory phosphatase, triggers protein degradation in adult muscle cells using a pre-existing proteolytic system. This activation is not suppressed by mutation in either of the known genes encoding FGF ligands (egl-17 or let-756) but is well suppressed when both are mutated, indicating that either ligand is sufficient and at least one is necessary for FGFR activation. Activity of the Ras pathway through mitogen-activated protein kinase (MAPK) is required to trigger protein degradation. This is the first report that degradation of intracellular protein can be triggered by a growth factor receptor using an identified signal transduction pathway. The data raise the possibility that FGF-triggered proteolysis may be relevant to muscle remodeling or dedifferentiation.
成纤维细胞生长因子（FGFs）及其受体介导的信号传导先前已被证明与细胞增殖、分化和迁移的控制有关。在此，我们报告秀丽隐杆线虫的EGL-15成纤维细胞生长因子受体（FGFR）信号传导在控制分化肌肉中的蛋白质降解方面具有新作用。通过影响抑制性磷酸酶的功能缺失突变（clr-1）激活EGL-15，利用现有的蛋白水解系统触发成年肌肉细胞中的蛋白质降解。这种激活不会被编码FGF配体的两个已知基因（egl-17或let-756）中的任何一个突变所抑制，但当两者都发生突变时则会被很好地抑制，这表明任何一种配体都足够，并且至少有一种对于FGFR激活是必需的。通过丝裂原活化蛋白激酶（MAPK）的Ras途径的活性是触发蛋白质降解所必需的。这是第一份关于生长因子受体利用已确定的信号转导途径触发细胞内蛋白质降解的报告。这些数据增加了FGF触发的蛋白水解可能与肌肉重塑或去分化相关的可能性。
