ArticleProceedings of the National Academy of Sciences of the United States of America2010
STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 88 citations in OpenAlex.
- The perinecrotic niche of glioblastoma drives tumor-associated macrophage polarization and immunosuppression via podoplanin-mediated CLEC5A activation.The Journal of clinical investigation · 2026Article
- Targeting SYK to alleviate MDSC-driven immunosuppression and augment anti-PD1 efficacy.Science China. Life sciences · 2026Article
- Neuronal Reg3β/macrophage TNF-α-mediated positive feedback signaling contributes to pain chronicity in a rat model of CRPS-I.Science advances · 2025Article
- Tyrosine kinases in KMT2A/MLL-rearranged acute leukemias as potential therapeutic targets to overcome cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- Nanomedicines in B cell-targeting therapies.Acta biomaterialia · 2022Review
- Spleen tyrosine kinase activity regulates epidermal growth factor receptor signaling pathway in ovarian cancer.EBioMedicine · 2019Article
- Contemporary patient-tailored treatment strategies against high risk and relapsed or refractory multiple myeloma.EBioMedicine · 2019Review
- Cell wall mannan of Candida krusei mediates dendritic cell apoptosis and orchestrates Th17 polarization via TLR-2/MyD88-dependent pathway.Scientific reports · 2018Article
- SYK Inhibition Induces Apoptosis in Germinal Center-Like B Cells by Modulating the Antiapoptotic Protein Myeloid Cell Leukemia-1, Affecting B-Cell Activation and Antibody Production.Frontiers in immunology · 2018Article
- SYK inhibition thwarts the BAFF - B-cell receptor crosstalk and thereby antagonizes Mcl-1 in chronic lymphocytic leukemia.Haematologica · 2017Article
- DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway.Cell death & disease · 2017Article
- Co-occurring protein phosphorylation are functionally associated.PLoS computational biology · 2017Article
- Extracellular matrix protein Reelin promotes myeloma progression by facilitating tumor cell proliferation and glycolysis.Scientific reports · 2017Article
- Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation.Cancer research · 2017Article
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- Reelin promotes the adhesion and drug resistance of multiple myeloma cells via integrin β1 signaling and STAT3.Oncotarget · 2016Article
- Pancreas-protective effect of rituximab for acute-onset type 1 diabetes in the honeymoon period: a case report.Endocrinology, diabetes & metabolism case reports · 2016Article
- Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy.The Journal of biological chemistry · 2015Article
- Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules.Cancer cell · 2015Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We provide unprecedented genetic and biochemical evidence that the antiapoptotic transcription factor STAT3 serves as a substrate for SYK tyrosine kinase both in vitro and in vivo. Induction of SYK in an ecdysone-inducible mammalian expression system results in STAT3 activation, as documented by tyrosine phosphorylation and nuclear translocation of STAT3, as well as amplified expression of several STAT3 target genes. STAT3 activation after oxidative stress (OS) is strongly diminished in DT40 chicken B-lineage lymphoma cells rendered SYK-deficient by targeted disruption of the syk gene. Introduction of a wild-type, C-terminal or N-terminal SH2 domain-mutated, but not a kinase domain-mutated, syk gene into SYK-deficient DT40 cells restores OS-induced enhancement of STAT-3 activity. Thus, SYK plays an important and indispensable role in OS-induced STAT3 activation and its catalytic SH1 domain is critical for this previously unknown regulatory function. These results provide evidence for the existence of a novel mode of cytokine-independent cross-talk that operates between SYK and STAT3 pathways and regulates apoptosis during OS. We further provide experimental evidence that SYK is capable of associating with and phosphorylating STAT3 in human B-lineage leukemia/lymphoma cells challenged with OS. In agreement with a prerequisite role of SYK in OS-induced STAT3 activation, OS does not induce tyrosine phosphorylation of STAT3 in SYK-deficient human proB leukemia cells. Notably, inhibition of SYK with a small molecule drug candidate prevents OS-induced activation of STAT3 and overcomes the resistance of human B-lineage leukemia/lymphoma cells to OS-induced apoptosis.
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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.