Tyrosine kinases Lyn and Syk regulate B cell receptor‐coupled Ca2+ mobilization through distinct pathways.
Open accessAbstract
Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Lyn, Fyn, Blk or Lck) and Syk kinase. To dissect the functional roles of these two types of kinase in BCR signaling, lyn-negative and syk-negative B cell lines were established. Syk-deficient B cells abolished the tyrosine phosphorylation of phospholipase C-gamma 2, resulting in the loss of both inositol 1,4,5-trisphosphate (IP3) generation and calcium mobilization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed and slow Ca2+ mobilization, despite the normal kinetics of IP3 turnover. These results demonstrate that Syk mediates IP3 generation, whereas Lyn regulates Ca2+ mobilization through a process independent of IP3 generation.
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In cells expressing PLCγ2 R665W, the BCR-mediated increase in Ca2+ was sensitive to pharmacologic inhibitors of Syk and Lyn.
“In cells expressing PLC␥ 2 R665W , the BCR-mediated increase in Ca 2ϩ was sensitive to pharmacologic inhibitors of Syk and Lyn, signaling components previously known to be essential for BCR-mediated InsP 3 generation and rapid Ca 2ϩ mobilization, respectively, in DT40 cells (47).”
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- Authors
- Takata, M., Sabe, H., Hata, A., Inazu, T., Homma, Y., Nukada, T., Yamamura, H., & Kurosaki, T.
- Venue
- The EMBO Journal
- Published
- 1994-03-01
- Volume
- 13
- Issue
- 6
- Pages
- 1341-1349
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC394950
- OpenAlex
- W136542906
- Cited by
- 650
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 9 · 2016: 11 · 2015: 11 · 2014: 13 · 2013: 14 · 2012: 15
- FWCI
- 25.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- Lyn kinase, Syk, B cell receptor signaling, calcium mobilization, PLCγ2, inositol 1,4,5-trisphosphate, Src family kinases, tyrosine phosphorylation, B cells
- MeSH terms
- Syk Kinase, Animals, Calcium, Cells, Cultured, Chickens, Enzyme Precursors, Phosphatidylinositols, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Inositol 1,4,5-Trisphosphate, src-Family Kinases, Intracellular Signaling Peptides and Proteins
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