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Mechanism of B-Cell Receptor-Induced Phosphorylation and Activation of Phospholipase C-γ2
Open accessAbstract
Phospholipase C-gamma2 (PLC-gamma2) plays an important role in B-cell signaling. Phosphorylation of various tyrosine residues of PLC-gamma2 has been implicated in regulation of its lipase activity. With the use of antibodies specific for each of the putative phosphorylation sites, we have now shown that PLC-gamma2 is phosphorylated on Y753, Y759, and Y1217 in response to engagement of the B-cell receptor in Ramos cells, as well as in murine splenic B cells. In cells stimulated maximally via this receptor, the extent of phosphorylation of Y1217 was three times that of Y753 or of Y759. Stimulation of Jurkat T cells or platelets via their immunoreceptors also elicited phosphorylation of Y753 and Y759 but not that of Y1217. A basal level of phosphorylation of Y753 was apparent in unstimulated lymphocytes. The extent of phosphorylation of Y753 and Y759, but not that of Y1217, correlated with the lipase activity of PLC-gamma2. Examination of the effects of various pharmacological inhibitors and of RNA interference in Ramos cells suggested that Btk is largely, but not completely, responsible for phosphorylation of Y753 and Y759, whereas phosphorylation of Y1217 is independent of Btk. Finally, phosphorylation of Y1217 and that of Y753 and Y759 occurred on different PLC-gamma2 molecules.
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“PLCγ2 would then be phosphorylated at four tyrosines (Y753, Y759, Y1197, and Y1217 (8, 9, 10, 11)).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [10]
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“For example, in B-cells, phosphorylation of the Tyr759 in the regulatory array (cSH2-SH3 linker) correlates with the PLCγ2 activation and is largely mediated by Btk tyrosine kinase.”
From Characterisation of molecular mechanisms for PLCγ2 disease-linked variants (2024) · cites this paper as Kim et al., 2004
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“In contrast, phosphorylation of Tyr1217 in the C-terminal extension, didn't correlate with the PLC activity (Kim et al., 2004).”
From Characterisation of molecular mechanisms for PLCγ2 disease-linked variants (2024) · cites this paper as Kim et al., 2004
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Metadata
- Authors
- Kim, Y. J., Sekiya, F., Poulin, B., Bae, Y. S., & Rhee, S. G.
- Affiliations
- National Institutes of Health (US)
- Ewha Womans University (KR)
- Corresponding author
- Rhee, Sue Goo
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-11
- Volume
- 24
- Issue
- 22
- Pages
- 9986-9999
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC525462
- OpenAlex
- W2137816745
- Cited by
- 126
- References
- 55
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 7 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 8 · 2013: 3 · 2012: 8
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- PLCγ2, B cell receptor signaling, tyrosine phosphorylation, Bruton's tyrosine kinase, lipase activity, Ramos cells, splenic B cells, T cell receptor signaling, RNA interference
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Amino Acid Sequence, Animals, Antibodies, B-Lymphocytes, Binding Sites, Cell Line, Enzyme Activation, Humans, Molecular Sequence Data, Type C Phospholipases, Phosphorylation, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Sequence Homology, Amino Acid, Jurkat Cells, RNA Interference, Mice, Phospholipase C gamma, In Vitro Techniques
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