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https://doi.org/10.7554/elife.68678
Title: | Src activates retrograde membrane traffic through phosphorylation of GBF1 | Authors: | Chia, Joanne Wang, Shyi-Chyi Wee, Sheena Gill, David James Tay, Felicia Kannan, Srinivasaraghavan Verma, Chandra S. Gunaratne, Jayantha Bard, Frederic A. |
Issue Date: | 6-Dec-2021 | Publisher: | eLife Sciences Publications Ltd | Citation: | Chia, Joanne, Wang, Shyi-Chyi, Wee, Sheena, Gill, David James, Tay, Felicia, Kannan, Srinivasaraghavan, Verma, Chandra S., Gunaratne, Jayantha, Bard, Frederic A. (2021-12-06). Src activates retrograde membrane traffic through phosphorylation of GBF1. eLife 10 : e68678. ScholarBank@NUS Repository. https://doi.org/10.7554/elife.68678 | Rights: | Attribution 4.0 International | Abstract: | 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. The kinase phosphorylates 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 GBF1 binding to the GTPase; molecular modeling suggests partial melting of the Sec7 domain and intramolecular rearrangement. GBF1 mutants defective for these rearrangements prevent binding, carrier formation, and GALNTs relocation, while phosphomimetic GBF1 mutants induce tubules. In sum, Src promotes GALNTs relocation by promoting GBF1 binding to Arf1. Based on residue conservation, similar regulation of GEF-Arf complexes by tyrosine phosphorylation could be a conserved and widespread mechanism. © Chia et al. | Source Title: | eLife | URI: | https://scholarbank.nus.edu.sg/handle/10635/233002 | ISSN: | 2050-084X | DOI: | 10.7554/elife.68678 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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