ArticleThe EMBO journal2001
The non-receptor tyrosine kinase Syk is a target of Cbl-mediated ubiquitylation upon B-cell receptor stimulation.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 133 citations in OpenAlex.
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- Phosphorylation at Y317 on Syk negatively regulates both ITAM- and hemITAM-mediated signaling and function in platelets.Blood advances · 2025Article
- Rescuing natural killer cells from the cancer wilderness.Journal for immunotherapy of cancer · 2025Article
- The Ubiquitin-Associated and SH3 Domain-Containing Proteins (UBASH3) Family in Mammalian Development and Immune Response.International journal of molecular sciences · 2024Review
- Article
- TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family.International journal of molecular sciences · 2023Review
- TULA-Family Regulators of Platelet Activation.International journal of molecular sciences · 2022Review
- IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK.Leukemia · 2021Article
- Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions.Biomolecules · 2021Article
- The combination of FLT3 and SYK kinase inhibitors is toxic to leukaemia cells with CBL mutations.Journal of cellular and molecular medicine · 2020Article
- The regulators of BCR signaling during B cell activation.Blood science (Baltimore, Md.) · 2019Review
- The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-κB p65 translocation.Journal of cellular and molecular medicine · 2019Article
- Article
- Structural Determinants of the Gain-of-Function Phenotype of Human Leukemia-associated Mutant CBL Oncogene.The Journal of biological chemistry · 2017Article
- Article
- Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection.The Journal of biological chemistry · 2015Article
- Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Signaling mechanisms regulating B-lymphocyte activation and tolerance.Journal of molecular medicine (Berlin, Germany) · 2015Review
- TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function.Cellular and molecular life sciences : CMLS · 2013Article
- Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases.Biochimica et biophysica acta · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The negative regulator Cbl functions as a ubiquitin ligase towards activated receptor tyrosine kinases and facilitates their transport to lysosomes. Whether Cbl ubiquitin ligase activity mediates its negative regulatory effects on cytoplasmic tyrosine kinases of the Syk/ZAP-70 family has not been addressed, nor is it known whether these kinases are regulated via ubiquitylation during lymphocyte B-cell receptor engagement. Here we show that B-cell receptor stimulation in Ramos cells induces the ubiquitylation of Syk tyrosine kinase which is inhibited by a dominant-negative mutant of Cbl. Intact tyrosine kinase-binding and RING finger domains of Cbl were found to be essential for Syk ubiquitylation in 293T cells and for in vitro Syk ubiquitylation. These same domains were also essential for Cbl-mediated negative regulation of Syk as measured using an NFAT-luciferase reporter in a lymphoid cell. Association with Cbl did not alter the kinase activity of Syk. Altogether, our results support an essential role for Cbl ubiquitin ligase activity in the negative regulation of Syk, and establish that ubiquitylation provides a mechanism of Cbl-mediated negative regulation of cytoplasmic targets.
Indexed as
Identifiers
What OpenQuestion holds
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.