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syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction
Open accessAbstract
Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well.
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“Once recruited to the DAP12 ITAM motif, Syk is phosphorylated by Src on its activation loop and this then initiates an autophosphorylation of other Syk molecules [69]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [69]
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Cites
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Self-citationSrc Family Protein Tyrosine Kinases Induce Autoactivation of Bruton's Tyrosine Kinase
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Cited by
Sorted by citations
THE HIGH-AFFINITY I g E RECEPTOR (FcεRI): From Physiology to Pathology
Kinet, J.-P. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.931 · Cited by 968
Self-citationSignalling through the high-affinity IgE receptor FcεRI
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“This step enables the productive interaction of active Syk with its many target”
BackgroundSelf-citationRegulation of mast-cell and basophil function and survival by IgE
Kawakami, T., & Galli, S. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri914 · Cited by 632
New developments in FcεRI regulation, function and inhibition
Kraft, S., & Kinet, J. (2007) · Nature reviews. Immunology · doi:10.1038/nri2072 · Cited by 580
Self-citationFyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation
Parravicini, V., Gadina, M., Kovářová, M., Odom, S., González‐Espinosa, C., Furumoto, Y., Saitoh, S.-I., Samelson, L. E., O’Shea, J. J., & Rivera, J. (2002) · Nature Immunology · doi:10.1038/ni817 · Cited by 449
Metadata
- Authors
- El-Hillal, O., Kurosaki, T., Yamamura, H., Kinet, J.-P., & Scharenberg, A. M.
- Affiliations
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-03-04
- Volume
- 94
- Issue
- 5
- Pages
- 1919-1924
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC20018
- OpenAlex
- W2036431526
- Cited by
- 130
- References
- 24
- Citations by year
- 2026: 1 · 2024: 6 · 2023: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (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 › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- Syk, kinase activation, Src family kinases, activation loop phosphorylation, Fc receptors, antigen receptor signaling, Bruton's tyrosine kinase, Tec family kinases
- MeSH terms
- Syk Kinase, Animals, Cell Line, Enzyme Activation, Enzyme Precursors, Gene Expression Regulation, Kinetics, Peptide Mapping, Phosphopeptides, Phosphorylation, Protein-Tyrosine Kinases, Receptors, Fc, Swine, Transfection, Tyrosine, Vaccinia virus, Blotting, Western, 3T3 Cells, src Homology Domains, src-Family Kinases, Intracellular Signaling Peptides and Proteins, Mice
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