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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 Shekhar
Gunaratne, Jayantha
Bard, Frederic A.
Keywords: Science::Biological sciences
Issue Date: 2021
Source: Chia, J., Wang, S., Wee, S., Gill, D. J., Tay, F., Kannan, S., Verma, C. S., Gunaratne, J. & Bard, F. A. (2021). Src activates retrograde membrane traffic through phosphorylation of GBF1. ELife, 10, e68678-.
Journal: eLife
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.
ISSN: 2050-084X
DOI: 10.7554/eLife.68678
Schools: School of Biological Sciences 
Organisations: Bioinformatics Institute, A*STAR
National University of Singapore
Rights: © 2021 Chia et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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