Negative regulation of FGFR3 signaling

Once activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-mediated inhibition of FRS2-tyrosine phosphorylation and the attenuation of ERK signaling through the action of dual-specificity phosphatases, IL17RD/SEF, Sprouty and Spred proteins. A number of these inhibitors are themselves transcriptional targets of the activated FGFR pathway.

一旦激活，FGFR信号通路便受到多种负反馈机制的调节。这些机制包括通过CBL介导的泛素化和内吞作用下调受体，通过ERK介导的FRS2酪氨酸磷酸化抑制以及通过双特异性磷酸酶、IL17RD/SEF、Sprouty和Spred蛋白的作用来减弱ERK信号传导。其中，许多抑制剂本身也是激活的FGFR通路转录靶点。