Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/163921
Title: Bruton's tyrosine kinase phosphorylates scaffolding and RNA-binding protein G3BP1 to induce stress granule aggregation during host sensing of foreign ribonucleic acids
Authors: Kim, Susana S-Y.
Sim, Don C. N.
Carissimo, Guillaume
Lim, Hong-Hwa
Lam, Kong-Peng
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Kim, S. S., Sim, D. C. N., Carissimo, G., Lim, H. & Lam, K. (2022). Bruton's tyrosine kinase phosphorylates scaffolding and RNA-binding protein G3BP1 to induce stress granule aggregation during host sensing of foreign ribonucleic acids. Journal of Biological Chemistry, 298(8), 102231-. https://dx.doi.org/10.1016/j.jbc.2022.102231
Project: OF-YIRG19MAY-0014
Journal: Journal of Biological Chemistry
Abstract: The Ras-GTPase activating protein SH3 domain-binding protein 1 (G3BP1) plays a critical role in the formation of classical and antiviral stress granules in stressed and virus-infected eukaryotic cells, respectively. While G3BP1 is known to be phosphorylated at serine residues which could affect stress granule assembly, whether G3BP1 is phosphorylated at tyrosine residues and how this posttranslational modification might affect its functions is less clear. Here, we show using immunoprecipitation and immunoblotting studies with 4G10 antibody that G3BP1 is tyrosine-phosphorylated when cells are stimulated with the synthetic double-stranded RNA analog polyinosinic:polycytidylic acid to mimic viral infection. We further demonstrate via co-immunoprecipitation and inhibitor studies that Bruton's tyrosine kinase (BTK) binds and phosphorylates G3BP1. The nuclear transport factor 2-like domain of G3BP1 was previously shown to be critical for its self-association to form stress granules. Our mass spectrometry, mutational and biochemical cross-linking analyses indicate that the tyrosine-40 residue in this domain is phosphorylated by BTK and critical for G3BP1 oligomerization. Furthermore, as visualized via confocal microscopy, pretreatment of cells with the BTK inhibitor LFM-A13 or genetic deletion of the btk gene or mutation of G3BP1-Y40 residue to alanine or phenylalanine all significantly attenuated the formation of antiviral stress granule aggregates upon polyinosinic:polycytidylic acid treatment. Taken together, our data indicate that BTK phosphorylation of G3BP1 induces G3BP1 oligomerization and facilitates the condensation of ribonucleoprotein complexes into macromolecular aggregates.
URI: https://hdl.handle.net/10356/163921
ISSN: 0021-9258
DOI: 10.1016/j.jbc.2022.102231
Rights: © 2022 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Page view(s)

22
Updated on Feb 1, 2023

Download(s)

3
Updated on Feb 1, 2023

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.