Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Janus tyrosine kinase (JAK) has recently been linked to signal transduction by cytokine receptors of the hematopoietin family. We have recently described a 116-kDa tyrosine kinase (p116) present in interleukin-2 (IL-2) receptor complexes in human YT cells that showed functional characteristics of a JAK kinase. These included receptor association, rapid and transient tyrosine phosphorylation kinetics in response to ligand, and in vitro autophosphorylating tyrosine kinase activity (Kirken, R. A., Rui, H., Evans, G. A., and Farrar, W. L. (1993) J. Biol. Chem. 268, 22765-22770). Here we extend these observations by demonstrating structural homologies between IL-2-modulated p116 and prolactin-modulated JAK2 in the rat T cell line Nb2. These include similar net charge as determined by nonequilibrium pH gradient electrofocusing and related primary structure based upon phosphopeptide mapping of V8 protease-digested hyperphosphorylated proteins. This putative JAK kinase underwent marked tyrosine phosphorylation in response to IL-2, IL-4, and IL-7, lymphoid growth factors that use the common IL-2 receptor gamma-chain, but not in response to prolactin. Furthermore, polyclonal antisera to JAK1, JAK2, or tyrosine kinase 2 did not recognize either rat or human p116. However, we identified the IL-2-modulated p116 as the recently cloned novel leukocyte Janus kinase, L-JAK, using an antiserum to a peptide corresponding to the COOH terminus of human L-JAK.
 ...
PMID:Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase. 751 51

Treatment of pregnant Long Evans rats with benzodiazepines was found to cause alterations in cellular immune responses in their offspring. We now report on changes in interleukin-1 (IL-1) and IL-2 secretion which were analyzed in rats from birth until 12 weeks. Time-pregnant rats were treated with diazepam (1.25 mg/kg/day subcutaneously) from gestational day 14 to 20. Lipopolysaccharide-stimulated release of macrophage-derived IL-1 by spleen cells, determined on D10.G4.1 cells, remained in the control range during the preweaning period (postnatal day 6-28), then decreased in prenatally diazepam-exposed offspring, significantly in males during the postweaning period (postnatal day 34-61) and in both sexes in adults (postnatal day 62-83). Concanavalin A-stimulated release of T lymphocyte-derived IL-2 from spleen cells, determined on CTLL-2 cells, was reduced in male and female offspring during preweaning (postnatal day 3-28) and postweaning (postnatal day 33-55) periods and normalized in adulthood (postnatal day 60-84). The percentage of IL-2 receptor expressing (CD25+) cells was unaffected. From these and our earlier data it is evident that prenatal exposure to low doses of benzodiazepines can result in long-lasting alterations of the cytokine network, as indicated by reduced release of TNF-alpha, IL-1, IL-6, IL-2 and interferon-gamma. The concomitant reduction of peripheral type benzodiazepine receptors on macrophages is discussed as a possible link between prenatal treatment and disturbed function.
 ...
PMID:Diazepam treatment of pregnant rats differentially affects interleukin-1 and interleukin-2 secretion in their offspring during different phases of postnatal development. 815 57

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that is considered to be a potent immunotoxicant. In the present study, we examined the effect of 25 micrograms/kg TCDD on cytokine production and T lymphocyte phenotype, cell cycling and receptor activity in female Long-Evans rats that had been injected with 50 micrograms of Staphylococcal Enterotoxin B (SEB). In the SEB-injected rats, TCDD increased the serum levels of interleukin-2 (IL-2) but did not affect the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) or tumor necrosis factor (TNF). The ability of spleen cells and peritoneal cells to produce cytokines in response to SEB restimulation in vitro was also evaluated. TCDD exposure significantly enhanced IL-2 production by spleen cells from SEB-primed rats after 6 h or 24 h in cultures co-stimulated with SEB in vitro. However, TCDD treatment did not alter the production of IL-6 and TNF in these cultures. Although TCDD did not influence the production of IL-6 and TNF in peritoneal cells from SEB-primed rats with SEB restimultion in vitro, IL-1 production was significantly increased at 2 h. Both the kinetics and extent of SEB-induced IL-2 receptor (IL-2R) and T-cell receptor (TCR) expression on CD4+ cells was unaffected by TCDD. TCDD did not significantly alter the percentage or the total numbers of CD4+ and CD8+ subpopulations at various times after SEB injection. However, flow cytometric analysis showed that TCDD exposure increased the percentage of both CD4+ and CD8+ cells cycling in the S and G2M phase. TCDD, in the absence of SEB priming, did not affect any of the immune parameters tested. Nevertheless, collectively these results showed that TCDD can enhance the production of IL-2 and the percentage of CD4+ and CD8+ cells cycling in SEB-exposed Long-Evans rats. Histopatholgically, there were not observable effects of SEB on lymphoid organs while thymic atrophy and diffuse hepatocellular hypertrophy was observed in the TCDD-treated animals.
 ...
PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin co-stimulates staphylococcal enterotoxin beta (SEB) cytokine production and phenotypic cell cycling in Long-Evans rats. 971 81