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

The objective of the present investigation was to define a more precise role for intracellular polyamine biosynthesis with respect to specific inducible events which regulate lymphocyte mitogenesis. In this regard, we have examined the effect of polyamine depletion on interleukin 2 (IL-2) production, receptor expression, and responsiveness in Con A stimulated mononuclear leukocytes (MNL). Polyamine depletion was achieved utilizing the specific irreversible inhibitor of ornithine decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO). Polyamine depletion of MNL augmented detectable levels of Con A-induced IL-2 activity. In contrast, the ability of polyamine depleted MNL to respond to saturating levels of IL-2 (100 U/ml) following 72 or 96 hr of Con A stimulation was reduced 100 and 81%, respectively. Nonetheless, polyamine depletion did not impair the induction of IL-2 receptor expression. High-affinity IL-2 receptor density in the polyamine depleted population was greater than control cells late in culture (96 hr). The expression of high-affinity IL-2 receptors did not correlate with an ability to respond to IL-2 in the polyamine depleted population. The results of this study demonstrate for the first time that intracellular polyamine biosynthesis is required for IL-2 responsiveness during a primary mitogenic lymphocyte response.
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PMID:Intracellular polyamine biosynthesis is required for interleukin 2 responsiveness during lymphocyte mitogenesis. 310 98

DL-alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase [EC 4.1.1.17] (ODC), inhibited concanavalin A-induced proliferation of splenic mononuclear cells (SMNC). The inhibition was not reversed by interleukin-2 (IL-2) addition. Although DFMO did not affect the production of IL-2 or the expression of high-affinity IL-2 receptor, IL-2-dependent proliferation of SMNC was inhibited by DFMO, and the inhibition was reversed by exogenous putrescine. The inhibition of IL-2-dependent DNA synthesis appeared to be related to the decrease in intracellular polyamines. When the proliferation of SMNC was induced by IL-2, ODC activity was also increased. A similar result was obtained in the proliferation of an IL-2-dependent T cell line, CTLL. The time course of ODC induction was similar to that of IL-2 production by concanavalin A-stimulated SMNC. These results indicate that polyamine biosynthesis is necessary for IL-2-dependent proliferation, but not for IL-2 production or IL-2 receptor expression.
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PMID:Polyamine biosynthesis is necessary for interleukin-2-dependent proliferation but not for interleukin-2 production or high-affinity interleukin-2 receptor expression. 312 15

In order to investigate the mechanisms by which cytokines and tumor promoters stimulate cell growth, the expression of genes implicated in the regulation of cellular proliferation were examined in an interleukin-3 (IL-3) dependent hematopoietic cell line. Upon stimulation of factor-deprived cells with IL-3, mRNA transcripts encoding the immediate-early genes: c-myc, jun-B, krox-20, beta-actin, and the cytokine genes: IL-4 and IL-6 were detected within 1 h. In contrast mRNA transcripts encoding the delayed-early genes: ornithine decarboxylase, p53, the IL-2 receptor-alpha, IL-4 receptor, and the T cell receptor c-gamma chains were observed at highest levels later. The tumor promoter, phorbol 12-myristate 13-acetate also stimulated the expression of many immediate-early genes, however, c-myc and the delayed-early genes were only detected when IL-3 was present. We conclude that cytokines and tumor promoters have distinct effects on proto-oncogene expression in hematopoietic cells which may affect the ability of these agents to promote cellular growth versus differentiation.
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PMID:Differential-effects of tumor promoters and cytokines on protooncogene expression in a hematopoietic cytokine-dependent cell-line. 2160 54