ArticleMolecular and cellular biology2006
Negative regulation of interleukin-2 and p38 mitogen-activated protein kinase during T-cell activation by the adaptor ALX.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation.Science signaling · 2019Article
- Host responses to live-attenuated Venezuelan equine encephalitis virus (TC-83): comparison of naïve, vaccine responder and nonresponder to TC-83 challenge in human peripheral blood mononuclear cells.Human vaccines & immunotherapeutics · 2012Article
- Differential expression of the adaptor protein HSH2 controls the quantitative and qualitative nature of the humoral response.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Phosphorylation at serine 318 is not required for inhibition of T cell activation by ALX.Biochemical and biophysical research communications · 2010Article
- Adapters in the organization of mast cell signaling.Immunological reviews · 2009Review
- Regulation of lymphocyte development and activation by the LAT family of adapter proteins.Immunological reviews · 2009Review
- Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Genetic analysis of SH2D4A, a novel adapter protein related to T cell-specific adapter and adapter protein in lymphocytes of unknown function, reveals a redundant function in T cells.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Asbestos-induced MKP-3 expression augments TNF-alpha gene expression in human monocytes.American journal of respiratory cell and molecular biology · 2008Article
- Rapid transit in the immune cells: the role of mRNA turnover regulation.Journal of leukocyte biology · 2007Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Activation of naïve T cells requires synergistic signals produced by the T-cell receptor (TCR) and by CD28. We previously identified the novel adaptor ALX, which, upon overexpression in Jurkat T cells, inhibited activation of the interleukin-2 (IL-2) promoter by TCR/CD28, suggesting that it is a negative regulator of T-cell activation. To further understand the physiological role of ALX, ALX-deficient mice were generated. Purified T cells from ALX-deficient mice demonstrated increased IL-2 production, CD25 expression, and proliferation in response to TCR/CD28 stimulation. Enhanced IL-2 production and proliferation were also observed when ALX-deficient mice were primed in vivo with ovalbumin-complete Freund's adjuvant and then restimulated ex vivo. Consistent with our initial overexpression studies, these data demonstrate that ALX is a negative regulator of T-cell activation. While TCR/CD28-mediated activations of phosphotyrosine induction, extracellular signal-regulated kinase 1/2, Jun N-terminal protein kinase, IkappaB kinase alpha/beta, and Akt were unaltered, constitutive activation of p38 mitogen-activated protein kinase and its upstream regulators MKK3/6 were observed for ALX-deficient splenocytes. The phenotype of ALX-deficient mice resembled the phenotype of those deficient in the transmembrane adaptor LAX, and an association between ALX and LAX proteins was demonstrated. These results suggest that ALX, in association with LAX, negatively regulates T-cell activation through inhibition of p38.
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