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Conserved roles for receptor tyrosine kinase extracellular regions in regulating receptor and pathway activity
Biochemical Journal ( IF 4.4 ) Pub Date : 2020-11-13 , DOI: 10.1042/bcj20200702
Monica Gonzalez-Magaldi 1 , Jacqueline M McCabe 2 , Haley N Cartwright 1 , Ningze Sun 1 , Daniel J Leahy 1, 2
Affiliation  

Receptor Tyrosine Kinases (RTKs) comprise a diverse group of cell-surface receptors that mediate key signaling events during animal development and are frequently activated in cancer. We show here that deletion of the extracellular regions of 10 RTKs representing 7 RTK classes or their substitution with the dimeric immunoglobulin Fc region results in constitutive receptor phosphorylation but fails to result in phosphorylation of downstream signaling effectors Erk or Akt. Conversely, substitution of RTK extracellular regions with the extracellular region of the Epidermal Growth Factor Receptor (EGFR) results in increases in effector phosphorylation in response to EGF. These results indicate that the activation signal generated by the EGFR extracellular region is capable of activating at least seven different RTK classes. Failure of phosphorylated Fc-RTK chimeras or RTKs with deleted extracellular regions to stimulate phosphorylation of downstream effectors indicates that either dimerization and receptor phosphorylation per se are insufficient to activate signaling or constitutive dimerization leads to pathway inhibition.

中文翻译:

受体酪氨酸激酶细胞外区域在调节受体和通路活性中的保守作用

受体酪氨酸激酶 (RTK) 包括一组不同的细胞表面受体,它们在动物发育过程中介导关键信号事件,并且在癌症中经常被激活。我们在此展示了代表 7 个 RTK 类别的 10 个 RTK 的细胞外区域的缺失或它们被二聚体免疫球蛋白 Fc 区域的取代会导致组成型受体磷酸化,但未能导致下游信号传导效应子 Erk 或 Akt 的磷酸化。相反,用表皮生长因子受体 (EGFR) 的细胞外区域替代 RTK 细胞外区域会导致响应于 EGF 的效应子磷酸化增加。这些结果表明 EGFR 胞外区产生的激活信号能够激活至少七种不同的 RTK 类别。
更新日期:2020-11-09
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