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)

We previously showed that an IL-2 mutant, Q126D, could induce T cells to proliferate to the same extent as wild-type IL-2 but was unable to sensitize T cells to activation-induced cell death (AICD). Here we show that the partial signaling of Q126D is attributable to its inability to up-regulate the IL-2 receptor alpha chain (CD25). IL-12, which can up-regulate CD25 expression, enhances the ability of Q126D to induce AICD sensitivity and proliferation. IL-12 synergism with Q126D is dependent on CD25 up-regulation because the synergism is absent in CD25-deficient T cells. Inhibition of IL-12-induced up-regulation of CD25 by a p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580, also ablates the synergism between IL-12 and Q126D. Although CD25 is important for IL-2-induced proliferation and AICD sensitivity, it is not absolutely required because a high concentration of IL-2 can overcome the requirement for CD25. Under physiological concentrations of IL-2, CD25 expression is critical for the function of IL-2. IL-12 can enhance the function of IL-2 by up-regulating CD25 in a p38 MAP kinase-dependent manner.
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PMID:IL-12 enhances IL-2 function by inducing CD25 expression through a p38 mitogen-activated protein kinase pathway. 1082 Mar 92

By comparing mature CD8-cell turnover in different organs, we previously demonstrated that CD8 cells proliferate predominantly in the bone marrow (BM). To investigate the mechanisms underlying such increased turnover, we compared BM, lymph nodes, and spleen CD8 cells from untreated C57BL/6 mice regarding in vivo proliferation within the organ; in vitro response to interleukin-7 (IL-7), IL-15, IL-21; ex vivo expression of membrane CD127 (IL-7Ralpha), intracellular Bcl-2, phospho-STAT-5 (signal transducer and activator of transcription 5), phospho-p38 mitogen activated protein kinase (MAPK); and in vivo proliferation on adoptive transfer. In the BM, the proliferation rate was increased for either total CD8 cells or individual CD44 and CD122 subsets. In contrast, purified CD8(+) cells from the BM did not show an enhanced in vitro proliferative response to IL-7, IL-15, and IL-21 compared with corresponding spleen cells. After transfer and polyinosinic-polycytidylic acid (polyI:C) treatment, both spleen-derived and BM-derived CD8 cells from congenic donors proliferated approximately twice more in the recipient BM than in spleen and lymph nodes. Our results suggest that BM CD8 cells are not committed to self-renewal, but rather are stimulated in the organ. Molecular events constantly induced in the CD8 cells within the BM of untreated mice include increase of both phosphorylated STAT-5 and phosphorylated p38 intracellular levels, and the reduction of CD127 membrane expression.
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PMID:Bone marrow CD8 cells down-modulate membrane IL-7Ralpha expression and exhibit increased STAT-5 and p38 MAPK phosphorylation in the organ environment. 1751 Mar 23