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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 recognition of the monocyte/macrophage-activating properties of IL-2 has broadened our image of the biological effects of this lymphokine from those of a T cell growth factor to those of a molecule with pleiotropic effects. The detailed analysis of the mechanisms of action of IL-2 including its biological effects on different cell types and the regulation of its receptors has increased dramatically the spectrum of the biological responses that can be modified by IL-2. The regulation of the expression of the IL-2 receptor subunits differs in terms of response to extracellular stimuli and intracellular control, suggesting that the response to IL-2 will vary depending on the nature and extent of environmental stimulation. Furthermore, the fact that the IL-2R gamma chain can be part of the receptor for IL-4, IL-7, and perhaps other cytokines indicates that IL-2 may modulate the response of monocytes simply by binding or releasing the IL-2R gamma chain and thus modulating the responsiveness to IL-4 or IL-7. Conversely, the extent of utilization of IL-2R gamma chain by various cytokines may dictate the monocytic response to IL-2. In fact, the availability of IL-2R gamma chain seems to be the limiting factor in the response of monocytes to IL-2. Modulation of cytokine receptors is an integral part of the control of the IL-2 response. The induction of CSF-1 receptor by IL-2 and the positive effect of CSF-1 on the duration of the cytotoxic response in IL-2-stimulated monocytes are an interesting example of a synergistic interaction of potential physiological relevance. The response of monocytes to IL-2 can also be modulated by inhibitory circuits, such as those involving TGF-beta 1, IFN-gamma, and IL-4. However, IFN-gamma and IL-4 can also activate monocytes and the timing and relative concentrations of the various cytokines may be critical variables in determining the ultimate monocyte phenotype. These studies have given us a glimpse of a very complex picture composed of multiple backgrounds and several players. However, the present information is not sufficient to make meaningful predictions of the resulting monocyte phenotype in an inflammatory reaction in which multiple cytokines are involved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin-2 and human monocyte activation. 782 65

The interleukin (IL)-2 receptor gamma chain has recently been shown to be a component of the IL-7 and IL-4 receptors. Using a transient transfection assay and the trans-activation of reporter gene constructs which are under the control of cytokine-responsive promoter elements, we have studied signal transduction through the IL-7 receptor (IL-7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the IL-7R, either as intact IL-7R or as part of a chimeric receptor. However, co-expression of the IL-7R with the IL-2 receptor gamma chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required.
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PMID:Reconstitution of a functional interleukin (IL)-7 receptor demonstrates that the IL-2 receptor gamma chain is required for IL-7 signal transduction. 787 1

Co-stimulation of highly purified peripheral T lymphocytes from healthy blood donors with the adhesion molecules CD2 and CD28 in association with recombinant interleukin-7 (rIL-7) induced T-cell proliferation, multiple cytokine secretion and IL-2 receptivity. We demonstrated that rIL-7 is as potent as rIL-2 in inducing the proliferation of unseparated, CD4+ and CD8+ T cells. In contrast to low or undetectable levels of IL-1 alpha, IL-6 and IL-2, high levels of tumour necrosis factor-alpha (TNF-alpha), IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were secreted. Experiments using blocking antibodies suggested a direct mechanism for rIL-7 co-stimulatory effect, although induction of the CD25/IL-2 receptor alpha-chain (CD25/IL-2R alpha) was observed. Monoclonal antibodies (mAb) against the adhesion molecules CD2 and CD28 are likely to mimic the interaction with their respective physiological ligands [lymphocyte function-associated antigen-3 (LFA-3)/CD58, CD59 and CD48 for CD2, B7/BB1 for CD28]. Taken together, these in vitro data suggest that IL-7 could participate in paracrine interactions between T lymphocytes and thymic stromal cells or dendritic cells, via its potent co-stimulatory activity with CD2 and CD28 adhesion molecules.
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PMID:Interleukin-7 is a potent co-stimulus of the adhesion pathway involving CD2 and CD28 molecules. 790 90

The interleukin-2 receptor plays a pivotal role in the regulation of the normal T cell immune response to foreign antigen. The IL-2 receptor gamma-chain is one component of this receptor, and is encoded by the gene that is defective in X-linked severe combined immunodeficiency. The clinical manifestations of this disease led to the hypothesis and subsequent confirmation that the gamma-chain was in fact a subunit shared by multiple cytokine receptors, including those for IL-2, IL-4, and IL-7.
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PMID:The defective gene in X-linked severe combined immunodeficiency encodes a shared interleukin receptor subunit: implications for cytokine pleiotropy and redundancy. 794 53

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.
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PMID:Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. 797 58

We have established two rat mAbs, TUGh4 and TUGh5, specific for the human gamma chain of the IL-2 receptor (IL-2R), which is known to be shared among receptors for IL-2, IL-4 and IL-7. The antibodies bound to cell lines transfected with the human gamma chain gene but not to their parental cell lines, and precipitated 65-70 and 80-90 kDa cell surface molecules from lysates of human T cells surface-labeled with Na125I and chemically cross-linked with [125I]IL-2 respectively. Flow cytometry with TUGh4 and TUGh5 detected the gamma chain in a wide variety of peripheral blood cell populations including CD4+ T cells, CD8+ T cells, CD20+ B cells, CD56+ natural killer cells, CD14+ monocytes and granulocytes, contrasting with expression of the alpha and beta chains of IL-2R.
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PMID:Expression of the IL-2 receptor gamma chain on various populations in human peripheral blood. 798 Nov 54

One important question in lymphopoiesis is where stem cells commit to T-, B- and natural killer (NK)-cell lineages. Recent findings in human and mouse systems suggest that the thymus is seeded by a yet uncommitted progenitor cell. The earliest murine thymic progenitor cells have the capacity to develop into B, T and NK cells when introduced into the appropriate microenvironment. The mechanisms underlying T-cell commitment are unknown, but cytokines might be involved. The gamma-chain of the interleukin (IL)-2 receptor seems to play a role in development of T and NK cells, but the current data argue against a critical role for IL-2 in T- and NK-cell development. This suggests that the IL-2 receptor gamma-chain is part of a receptor for another cytokine, important for T- and NK-cell development. IL-7 might be involved in regulating T-cell receptor rearrangements and in proliferation of cells within the thymus.
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PMID:Early stages in human and mouse T-cell development. 801 Dec 6

IL-2 regulates growth and differentiation of various types of cells in the immune system via its interaction with IL-2 receptor (IL-2R). The high and intermediate-affinity IL-2Rs, which consist of the alpha beta gamma heterotrimer complex and the beta gamma heterodimer complex, respectively, harbor the function of the intracellular signal transduction, indicating that the beta and gamma chains are indispensable for the signal transduction but not the alpha chain. The reconstitution studies of IL-2Rs with alpha, beta and gamma chain genes demonstrated that each subunit has potential for altering the affinity of the receptor, and the cytoplasmic domains of the beta and gamma chains participate in signal transduction in terms of cell growth, activation of alpha tyrosine kinase and enhancement of c-myc, c-fos and c-jun transcription. The region containing the SH2 homologous sequence of the gamma chain should have a critical function for signal transduction. On the other hand, common subunits are known to be shared among receptors for IL-3, IL-5 and GM-CSF, and receptors for IL-6, LIF, OSM and LIF. We have demonstrated that the monoclonal antibody specific for the IL-2R gamma chain completely inhibited not only IL-2-dependent cell growth but also IL-4-dependent, IL-7-dependent, and IL-9-dependent cell growth, suggesting that the gamma chain is possibly shared among receptors for IL-2, IL-4, IL-7 and IL-9. Impairment of the gamma chain function is considered to be closely related to human XSCID characterized by profound T cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Structure and function of IL-2 receptor subunits]. 802 15

We have recently cloned a novel cytokine, IL-15, with shared bioactivities but no sequence homology with IL-2. We found high affinity IL-15 binding to many cell types, including cells of non-lymphoid origin. Analysis of IL-15 interaction with subunits of the IL-2 receptor (IL-2R) revealed that the alpha subunit was not involved in IL-15 binding. We demonstrated directly in cells transfected with IL-2R subunits that both the beta and gamma chains are required for IL-15 binding and signaling. Hence, IL-15, like IL-2, IL-4 and IL-7, utilizes the common IL-2R gamma subunit found to be defective in X-linked severe combined immunodeficiency in humans. IL-15 is the only cytokine other than IL-2 that has also been shown to share the beta signaling subunit of IL-2R. The differential ability of some cells to bind and respond to IL-2 and IL-15 implies the existence of an additional IL-15-specific component.
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PMID:Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. 802 67

X-linked severe combined immunodeficiency is characterized by severe and persistent infections from early life resulting from profound impairment of both cellular and humoral immune function. XSCID is characterized by an absence or diminished number of T cells and histologic evidence of hypoplastic and abnormal differention of the thymic epithelium. The discovery that this disease results from the mutations of the IL-2R gamma chain was surprising since IL-2-deficient mice and human SCID patients had milder phenotypes. This led to the speculation that IL-2R gamma would prove to be a common gamma chain, gamma c, which would play important roles in other cytokine receptors in addition to the IL-2 receptor. There is now compelling evidence to support a role in at least two other cytokine receptors, namely the IL-4 and IL-7 receptors. Thus, with inactivation of gamma c, multiple cytokine systems are simultaneously affected, resulting in the profoundly impaired phenotype of XSCID. It is possible and even likely that gamma c will be found to be a functional component of additional receptors as well. These findings have resulted in a significant improvement in our understanding of the pathophysiologic development of the defects in XSCID and also have important ramifications for prenatal and postnatal diagnosis, carrier female identification, and gene therapy for XSCID.
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PMID:The molecular basis of X-linked severe combined immunodeficiency: the role of the interleukin-2 receptor gamma chain as a common gamma chain, gamma c. 807 Aug 18


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