Sef(similar expression to fgf genes)作为FGF信号通路中可诱导的拮抗分子相继在斑马鱼,小鼠,和人类中被鉴定出来,并进行了相应的功能研究.目前对于Sef蛋白本身稳定性的研究还未见报道.对c-Cbl对Sef稳定性的影响进行了研究.免疫荧光实...Sef(similar expression to fgf genes)作为FGF信号通路中可诱导的拮抗分子相继在斑马鱼,小鼠,和人类中被鉴定出来,并进行了相应的功能研究.目前对于Sef蛋白本身稳定性的研究还未见报道.对c-Cbl对Sef稳定性的影响进行了研究.免疫荧光实验表明Sef能够和c-Cbl蛋白在细胞中发生共定位,随后的免疫共沉淀实验证明Sef能够和c-Cbl发生相互作用.体内泛素化实验表明c-Cbl能够使Sef发生明显的泛素化作用.这种泛素化最终导致了Sef本身的剂量依赖性的降解.针对c-Cbl的siRNA表达也使Sef稳定细胞系的表达水平得到恢复.结果表明,c-Cbl对Sef的泛素化及降解可能作为一种调控拮抗因子的蛋白质水平从而最终调节信号通路的一种机制.展开更多
Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for...Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these processes. Activation of receptor tyrosine kinases by their cognate growth factors not only leads to propagation of the signal through various biochemical cascades, but also sets in motion multiple attenuation mechanisms that ulti- mately terminate the active state. Early attenuators pre-exist prior to receptor activation and they act to limit signal propagation. Subsequently, late attenuators, such as Lrig and Sprouty, are transcriptionally induced and further act to dampen the signal. Central to the process of signaling attenuation is the role of the E3 ubiquitin ligase c-Cbl. While Cbl- mediated processes of receptor ubiquitylation and endocytosis are relatively well understood, the links of Cbl to other negative regulators are just now beginning to be appreciated. Here we review some emerging interfaces between Cbl and the transcriptionally induced negative regulators Lrig and Sprouty.展开更多
文摘Sef(similar expression to fgf genes)作为FGF信号通路中可诱导的拮抗分子相继在斑马鱼,小鼠,和人类中被鉴定出来,并进行了相应的功能研究.目前对于Sef蛋白本身稳定性的研究还未见报道.对c-Cbl对Sef稳定性的影响进行了研究.免疫荧光实验表明Sef能够和c-Cbl蛋白在细胞中发生共定位,随后的免疫共沉淀实验证明Sef能够和c-Cbl发生相互作用.体内泛素化实验表明c-Cbl能够使Sef发生明显的泛素化作用.这种泛素化最终导致了Sef本身的剂量依赖性的降解.针对c-Cbl的siRNA表达也使Sef稳定细胞系的表达水平得到恢复.结果表明,c-Cbl对Sef的泛素化及降解可能作为一种调控拮抗因子的蛋白质水平从而最终调节信号通路的一种机制.
文摘Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these processes. Activation of receptor tyrosine kinases by their cognate growth factors not only leads to propagation of the signal through various biochemical cascades, but also sets in motion multiple attenuation mechanisms that ulti- mately terminate the active state. Early attenuators pre-exist prior to receptor activation and they act to limit signal propagation. Subsequently, late attenuators, such as Lrig and Sprouty, are transcriptionally induced and further act to dampen the signal. Central to the process of signaling attenuation is the role of the E3 ubiquitin ligase c-Cbl. While Cbl- mediated processes of receptor ubiquitylation and endocytosis are relatively well understood, the links of Cbl to other negative regulators are just now beginning to be appreciated. Here we review some emerging interfaces between Cbl and the transcriptionally induced negative regulators Lrig and Sprouty.
