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Src activates retrograde membrane traffic through phosphorylation of GBF1
bioRxiv - Cell Biology Pub Date : 2021-03-26 , DOI: 10.1101/2020.08.02.233353
Joanne Chia , Shyi-Chyi Wang , Sheena Wee , David James Gill , Felicia Tay , Srinivasaraghavan Kannan , Chandra S Verma , Jayantha Gunaratne , Frederic A. Bard

The Src tyrosine kinase controls cancer-critical protein glycosylation through Golgi to ER relocation of GALNTs enzymes. How Src induces this trafficking event is unknown. Golgi to ER transport depends on the GTP Exchange factor (GEF) GBF1 and small GTPase Arf1. Here we show that Src induces the formation of tubular transport carriers containing GALNTs through the activation of a GBF1-Arf1 complex. The complex is initiated by phosphorylation on GBF1 on 10 tyrosine residues; two of them, Y876 and Y898 are located near the C-terminus of the Sec7 GEF domain. Their phosphorylation promotes partial melting of the Sec7 domain, favoring binding to the GTPase. Perturbation of these rearrangements prevent GALNTs relocation. In sum, Src promotes GALNTs relocation by favoring binding of GBF1 to Arf1. Regulation of a GEF-Arf axis by tyrosine phosphorylation appears to be a highly conserved and wide-spread mechanism.

中文翻译:

Src通过GBF1的磷酸化激活逆行膜运输

Src酪氨酸激酶通过高尔基体对GALNTs酶的ER定位来控制癌症关键蛋白糖基化。Src如何引发此贩运事件尚不清楚。高尔基体到内质网的转运取决于GTP交换因子(GEF)GBF1和小的GTPase Arf1。在这里,我们显示Src通过GBF1-Arf1复合物的激活诱导包含GALNTs的管状运输载体的形成。该复合物是通过GBF1上10个酪氨酸残基的磷酸化作用引发的。Y876和Y898中的两个位于Sec7 GEF域的C端附近。它们的磷酸化促进Sec7结构域的部分融化,有利于与GTPase结合。这些重排的扰动阻止了GALNT的重新定位。总之,Src通过促进GBF1与Arf1的结合来促进GALNTs的重新定位。
更新日期:2021-03-26
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