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Phospholipase C-γ2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen
Open accessAbstract
B cell receptor (BCR) recognition of membrane-bound antigen initiates a spreading and contraction response, the extent of which is controlled through the formation of signaling-active BCR-antigen microclusters and ultimately affects the outcome of B cell activation. We followed a genetic approach to define the molecular requirements of BCR-induced spreading and microcluster formation. We identify a key role for phospholipase C-γ2 (PLCγ2), Vav, B cell linker, and Bruton's tyrosine kinase in the formation of highly coordinated “microsignalosomes,” the efficient assembly of which is absolutely dependent on Lyn and Syk. Using total internal reflection fluorescence microscopy, we examine at high resolution the recruitment of PLCγ2 and Vav to microsignalosomes, establishing a novel synergistic relationship between the two. Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation.
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“In addition to the production of IP3, DAG, and calcium flux, PLCγ2 activation results in activation of phospholipase D and cell spreading (12, 13, 14, 15, 16, 17), bringing on other vital cell signaling processes such as Erk (18).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [17]
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“Very interestingly, efficient assembly of the latter is absolutely dependent on Lyn and Syk (55).”
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Metadata
- Authors
- Weber, M., Treanor, B., Depoil, D., Shinohara, H., Harwood, N. E., Hikida, M., Kurosaki, T., & Batista, F. D.
- Affiliations
- Cancer Research UK (GB)
- RIKEN (JP)
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-03-24
- Volume
- 205
- Issue
- 4
- Pages
- 853-868
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2292224
- OpenAlex
- W2135715200
- Cited by
- 170
- References
- 84
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 13 · 2013: 13 · 2012: 10
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- PLCγ2, Vav, B cell receptor signaling, membrane-bound antigen, Bruton's tyrosine kinase, Lyn kinase, Syk, B cell activation, signal propagation
- MeSH terms
- Syk Kinase, Animals, Antigens, B-Lymphocytes, Cell Membrane, Cell Movement, Chickens, Models, Biological, Protein Binding, Protein-Tyrosine Kinases, Signal Transduction, src-Family Kinases, Intracellular Signaling Peptides and Proteins, Mice, Rats, Proto-Oncogene Proteins c-vav, Phospholipase C gamma, Inositol 1,4,5-Trisphosphate Receptors
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