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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin has been shown to enhance the proliferation and differentiation of T cells stimulated by both polyclonal stimulants and specific antigen. This study describes an experimental system designed to understand the mechanism(s) by which occupancy of the insulin receptor mediates the enhancement seen in T cell expansion. These experiments demonstrate that the ability of insulin to influence T cell expansion resides in an insulin-mediated maintenance of the interleukin-2 (IL-2) responsiveness of the activated cells. This was analyzed by following the decay pattern of T cell IL-2 responsiveness by placing the activated T cells into serum-free cultures in the presence or absence of insulin. This maintenance of responsiveness was not mediated by insulin regulating the expression of the IL-2 receptor alpha chain. We feel that this experimental approach will prove useful for dissecting the biochemical and molecular changes mediated by insulin which interface with the ability of activated T cells to effectively respond to IL-2.
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PMID:Insulin modulates the interleukin 2 responsiveness of T lymphocytes. 215 Sep 18

Our previous work examining the importance of insulin receptor (IR) expression on T cells has demonstrated that when T cells from nonobese diabetic mice were sorted into populations expressing a high (IR(High)) and a low (IR(Low)) density of IR, IR(High) T cells rapidly transferred insulitis and diabetes. We have further characterized IR(High) T cells. Both CD4+ and CD8+ cells were detected in the IR(High) T cell population, but IR(High) expression was detected predominantly on CD4+ cells. IRHigh T cells were polyclonal for TCR Vbeta-chain expression. By 3 color flow cytometric analysis, virtually all IR(High) T cells expressed low or negligible levels of CD62L (CD62L(Low)/-) and high levels of CD44 (CD44(High)). The lack of IL-2 receptor and transferrin receptor expression as seen previously, together with the CD62L(Low)/- CD44(High) phenotype suggests that IR(High) T cells are memory cells. However, since only about one quarter of all of the CD62L(Low)/- or CD44(High) T cells were also IR(High), the IR(High) phenotype defines a subpopulation of memory T cells that are aggressively diabetogenic.
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PMID:High density insulin receptor-positive diabetogenic T lymphocytes in nonobese diabetic mice are memory cells. 1095 38

Interleukins 9 (IL-9) and 4 are cytokines within the IL-2 receptor gamma chain (IL-2R gamma) superfamily that possess similar and unique biological functions. The signaling mechanisms, which may determine cytokine specificity and redundancy, are not well understood. IRS proteins are tyrosine-phosphorylated following IL-9 and IL-4 stimulation, a process in part mediated by JAK tyrosine kinases (Yin, T. G., Keller, S. R., Quelle, F. W., Witthuhn, B. A., Tsang, M. L., Lienhard, G. E., Ihle, J. N., and Yang, Y. C. (1995) J. Biol. Chem. 270, 20497--20502). In the present study, we used 32D cells stably transfected with insulin receptor (32D(IR)), which do not express any IRS proteins, as a model system to study the requirement of different structural domains of IRS proteins in IL-9- and IL-4-mediated functions. Overexpression of IRS-1 and IRS-2, but not IRS-4, induced proliferation of 32D(IR) cells in response to IL-9. The pleckstrin homology (PH) domain of IRS proteins is required for IRS-mediated proliferation stimulated by IL-9. The phosphotyrosine binding and Shc and IRS-1 NPXY binding domains are interchangeable for IRS to transduce the proliferative effect of IL-4. Therefore, the PH domain plays different roles in coupling IRS proteins to activated IL-9 and IL-4 receptors. The role of IRS proteins in determining cytokine specificity was corroborated by their ability to interact with different downstream signaling molecules. Although phosphatidylinositol 3' -kinase (PI3K) and Grb-2 interact with tyrosine-phosphorylated IRS proteins, Shp-2 only binds to IRS proteins following IL-4, but not IL-9, stimulation. Although PI3K activity is necessary for the IRS-1/2-mediated proliferative effect of IL-9 and IL-4, Akt activation is only required for cell proliferation induced by IL-4, but not IL-9. These data suggest that IRS-dependent signaling pathways work by recruiting different signaling molecules to determine specificity of IL-2R gamma superfamily cytokines.
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PMID:Specificity of interleukin-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathway. 1178 80