ArticleeLife2019
Unique-region phosphorylation targets LynA for rapid degradation, tuning its expression and signaling in myeloid cells.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 0 citations in OpenAlex.
- Cumulative expression of the two Lyn isoforms creates a threshold for macrophage signaling in the absence of receptor engagement.Journal of leukocyte biology · 2026Article
- Article
- A Biochemical Analysis of LINC00896 RNA in Cortex Neuronal Cells and Its Possible Connection to the Development of Autism.Journal of nucleic acids · 2026Article
- Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner.Journal of leukocyte biology · 2025Article
- The dualistic role of Lyn tyrosine kinase in immune cell signaling: implications for systemic lupus erythematosus.Frontiers in immunology · 2024Review
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- A phospho-tyrosine-based signaling module using SPOP, CSK, and LYN controls TLR-induced IRF activity.Science advances · 2022Article
- Role of inhibitory signaling in peripheral B cell tolerance.Immunological reviews · 2022Review
- A dominant function of LynB kinase in preventing autoimmunity.Science advances · 2022Article
- SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding.Scientific reports · 2022Article
- Regulation of myeloid-cell activation.Current opinion in immunology · 2021Review
- Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Src-family Kinase Lyn in Immunoreceptor Signaling.Endocrinology · 2021Review
- Immunopharmacology and Quantitative Analysis of Tyrosine Kinase Signaling.Current protocols in immunology · 2020Article
- Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The activity of Src-family kinases (SFKs), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs), is a critical factor regulating myeloid-cell activation. We reported previously that the SFK LynA is uniquely susceptible to rapid ubiquitin-mediated degradation in macrophages, functioning as a rheostat regulating signaling (Freedman et al., 2015). We now report the mechanism by which LynA is preferentially targeted for degradation and how cell specificity is built into the LynA rheostat. Using genetic, biochemical, and quantitative phosphopeptide analyses, we found that the E3 ubiquitin ligase c-Cbl preferentially targets LynA via a phosphorylated tyrosine (Y32) in its unique region. This distinct mode of c-Cbl recognition depresses steady-state expression of LynA in macrophages derived from mice. Mast cells, however, express little c-Cbl and have correspondingly high LynA. Upon activation, mast-cell LynA is not rapidly degraded, and SFK-mediated signaling is amplified relative to macrophages. Cell-specific c-Cbl expression thus builds cell specificity into the LynA checkpoint.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.