ArticleMolecular and cellular biology2000
Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 42 citations in OpenAlex.
- Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation.Inflammopharmacology · 2021Review
- Article
- Network pharmacology of JAK inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Pleiotropic Effects of IL-2 on Cancer: Its Role in Cervical Cancer.Mediators of inflammation · 2016Review
- MSCA: a spectral comparison algorithm between time series to identify protein-protein interactions.BMC bioinformatics · 2015Article
- Roles of TRAF3 in T cells: many surprises.Cell cycle (Georgetown, Tex.) · 2015Review
- The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2.Nature immunology · 2014Article
- Specific Jak3 Downregulation in Lymphocytes Impairs γc Cytokine Signal Transduction and Alleviates Antigen-driven Inflammation In Vivo.Molecular therapy. Nucleic acids · 2012Article
- JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and cell growth.Growth factors (Chur, Switzerland) · 2011Review
- Integrating signals from the T-cell receptor and the interleukin-2 receptor.PLoS computational biology · 2011Article
- Article
- Combinatorial Signal Transduction Responses Mediated by Interleukin-2 and -4 Receptors in a Helper TCellular and molecular bioengineering · 2008Article
- Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation.Blood · 2008Article
- Human immunodeficiency virus-1 envelope glycoproteins and anti-CD4 antibodies inhibit interleukin-2-induced Jak/STAT signalling in human CD4 T lymphocytes.Clinical and experimental immunology · 2003Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Interleukin-2 (IL-2) activates several different families of tyrosine kinases, but precisely how these kinases interact is not completely understood. We therefore investigated the functional relationships among Jak3, Lck, and Syk in IL-2 signaling. We first observed that in the absence of Jak3, both Lck and Syk had the capacity to phosphorylate Stat3 and Stat5a. However, neither supported IL-2-induced STAT activation, nor did dominant negative alleles of these kinases inhibit. Moreover, pharmacological abrogation of Lck activity did not inhibit IL-2-mediated phosphorylation of Jak3 and Stat5a. Importantly, ligand-dependent Syk activation was dependent on the presence of catalytically active Jak3, whereas Lck activation was not. Interestingly, Syk functioned as a direct substrate of Jak1 but not Jak3. Additionally, Jak3 phosphorylated Jak1, whereas the reverse was not the case. Taken together, our data support a model in which Lck functions in parallel with Jak3, while Syk functions as a downstream element of Jaks in IL-2 signaling. Jak3 may regulate Syk catalytic activity indirectly via Jak1. However, IL-2-mediated Jak3/Stat activation is not dependent on Lck or Syk. While the essential roles of Jak1 and Jak3 in signaling by gammac-utilizing cytokines are clear, it will be important to dissect the exact contributions of Lck and Syk in mediating the effects of IL-2 and related cytokines.
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