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Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction
Annual Review of Biochemistry ( IF 12.1 ) Pub Date : 2016-06-13 00:00:00 , DOI: 10.1146/annurev-biochem-060815-014659
John J.M. Bergeron 1 , Gianni M. Di Guglielmo 2 , Sophie Dahan 1 , Michel Dominguez 1 , Barry I. Posner 1
Affiliation  

Epidermal growth factor (EGF) and insulin receptor tyrosine kinases (RTKs) exemplify how receptor location is coupled to signal transduction. Extracellular binding of ligands to these RTKs triggers their concentration into vesicles that bud off from the cell surface to generate intracellular signaling endosomes. On the exposed cytosolic surface of these endosomes, RTK autophosphorylation selects the downstream signaling proteins and lipids to effect growth factor and polypeptide hormone action. This selection is followed by the recruitment of protein tyrosine phosphatases that inactivate the RTKs and deliver them by membrane fusion and fission to late endosomes. Coincidentally, proteinases inside the endosome cleave the EGF and insulin ligands. Subsequent inward budding of the endosomal membrane generates multivesicular endosomes. Fusion with lysosomes then results in RTK degradation and downregulation. Through the spatial positioning of RTKs in target cells for EGF and insulin action, the temporal extent of signaling, attenuation, and downregulation is regulated.

中文翻译:


受体酪氨酸激酶激活和细胞内信号转导的时空调控。

表皮生长因子(EGF)和胰岛素受体酪氨酸激酶(RTKs)体现了受体的位置如何与信号转导偶联。配体与这些RTK的胞外结合会触发其在囊泡中的浓度,这些囊泡会从细胞表面萌芽,从而生成胞内信号传递内体。在这些内体的暴露的胞质表面上,RTK自磷酸化作用选择下游的信号蛋白和脂质来影响生长因子和多肽激素的作用。该选择之后是募集蛋白酪氨酸磷酸酶,该酶使RTK失活,并通过膜融合和裂变将其递送至晚期内体。巧合的是,内体内部的蛋白酶裂解了EGF和胰岛素配体。内体膜的随后向内出芽产生多囊泡内体。然后与溶酶体融合导致RTK降解和下调。通过RTK在EGF和胰岛素作用靶细胞中的空间定位,可以调节信号传导,减弱和下调的时间范围。

更新日期:2016-06-13
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