Cross‐linking of the B cell receptor induces activation of phospholipase D through Syk, Btk and phospholipase C‐γ2
Open accessAbstract
Phospholipase D (PLD) has been proposed to play a key role in the signal transduction of cellular responses to various extracellular signals. Herein we provide biochemical and genetic evidence that cross-linking of the B cell receptor (BCR) induces rapid activation of PLD through a Syk-, Btk- and phospholipase C (PLC)-gamma2-dependent pathway in DT40 cells. Activation of PLD upon BCR engagement is completely blocked in Syk- or Btk-deficient cells, but unaffected in Lyn-deficient cells. Furthermore, in PLC-gamma2-deficient cells, BCR engagement failed to activate PLD. These results demonstrate that Syk, Btk and PLC-gamma2 are essential for BCR-induced PLD activation.
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PLCγ2 activation results in activation of phospholipase D and cell spreading, and brings on Erk signaling.
“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 [12]
The Results and discussion section shows that PLCγ2 is required for B-cell-receptor-induced phospholipase D activation in DT40 cells. Our copy does not address cell spreading. Erk signaling is attached to a separate citation (18) in the citing sentence, so it is not assessed as an attribution to this paper. (LLM, conf=0.88)
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The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration
Jackson, J. T., Mulazzani, E., Nutt, S. L., & Masters, S. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100905 · Cited by 113 · see citing works
Moreno-García, M. E., López-Bojórques, L. N., Zentella, A., Humphries, L. A., Rawlings, D. J., & Santos-Argumedo, L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.5.2687 · Cited by 54 · see citing works
- Authors
- Hitomi, T., Yanagi, S., Inatome, R., & Yamamura, H.
- Affiliations
- Kobe University (JP)
- Corresponding author
- Yamamura, Hirohei
- ORCID
- Yanagi, Shigeru
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1999-02-26
- Volume
- 445
- Issue
- 2-3
- Pages
- 371-374
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2064352346
- Cited by
- 26
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 1 · 2019: 1 · 2016: 2 · 2014: 2
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (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 › Cancer Research › NF-κB Signaling Pathways
- Keywords
- phospholipase D, B cell receptor, receptor cross-linking, Syk, Bruton's tyrosine kinase, PLCγ2, Lyn kinase, B cell activation, signal transduction, DT40 cells, tyrosine kinase signaling
- MeSH terms
- Syk Kinase, Agammaglobulinaemia Tyrosine Kinase, Animals, Cell Line, Cross-Linking Reagents, Enzyme Activation, Enzyme Precursors, Isoenzymes, Type C Phospholipases, Phospholipase D, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Intracellular Signaling Peptides and Proteins, Phospholipase C gamma
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