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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 IL-2 receptor complex is minimally composed of two genetically unrelated subunits of relative molecular masses 55 and 75 kDa respectively. Structural information deduced from the cDNA sequences of either subunit have not revealed significant information as to the basis of the mechanisms of IL-2 receptor signal transduction. Nevertheless, IL-2 stimulates the activation of one or more tyrosine kinases requiring the functional participation of the p75 member of the receptor complex. Here we have developed the methods to isolate the receptor complex with an associated tyrosine protein kinase. Extracts of membrane glycoproteins from activated normal human T lymphocytes and cell lines demonstrated catalytic activation of tyrosine kinase activity when stimulated with IL-2. Purification of the receptor complex with biotinylated IL-2 revealed the presence of two dominant phosphotyrosyl-proteins of approximate molecular masses 58 and 97 kDa. Denaturation gel electrophoresis followed by renaturation of proteins associated with the IL-2 receptor complex demonstrated that the 97 kDa protein had catalytic autophosphorylation activity. The results indicate that the 58 and 97 kDa phosphotyrosyl-proteins can be found to co-precipitate with the IL-2 receptor complex and that the 97 kDa protein was demonstrated to have protein kinase activity. The association of such kinases with receptors devoid of catalytic structure may represent a unique paradigm of growth-factor receptor mechanisms.
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PMID:Characterization of a tyrosine kinase activity associated with the high-affinity interleukin 2 receptor complex. 149 23

Interleukin 2 (IL-2) has been shown to stimulate tyrosine phosphorylation of a number of proteins requiring only the p75 beta chain of the IL-2 receptor. Unlike the receptors for epidermal growth factor, insulin, and other growth factors, the p55-alpha and p75-beta chains of the IL-2 receptor have no tyrosine protein kinase domain suggesting that the IL-2 receptor complex activates protein kinases by a unique mechanism. The activation of tyrosine kinases by IL-2 in situ was studied and using a novel methodology has shown tyrosine kinase activity associated with the purified IL-2R complex in vitro. IL-2 stimulated the in situ tyrosine phosphorylation of 97 kDa and 58 kDa proteins which bound to poly(Glu,Tyr)4:1, a substrate for tyrosine protein kinases, suggesting these proteins had characteristics found in almost all tyrosine kinases. IL-2 was found to stimulate tyrosine protein kinase activity in receptor extracts partially purified from human T lymphocytes and the YT cell line. Biotinylated IL-2 was used to precipitate the high-affinity-receptor complex and phosphoproteins associated with it. The data indicated that the 97-kDa and 58-kDa phosphotyrosyl proteins were tightly associated with the IL-2 receptor complex. These proteins were phosphorylated on tyrosine residues by IL-2 stimulation of intact cells and ligand treatment of in vitro receptor extracts. Furthermore, the 97-kDa and 58-kDa proteins were found in streptavidin-agarose/biotinylated IL-2 purified receptor preparations and showed high affinity for tyrosine kinase substrate support matrixes. The experiments suggest that these two proteins are potential candidates for tyrosine kinases involved in the IL-2R complex signal transduction process.
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PMID:Regulation of the interleukin 2 receptor complex tyrosine kinase activity in vitro. 175 80

Addition of interleukin 2 (IL-2) to IL-2-dependent T cells results in tyrosine protein kinase signal transduction events even though the IL-2 receptor alpha and beta chains lack intrinsic enzymatic activity. Here we report that addition of IL-2 to IL-2-dependent human T cells transiently stimulates the specific activity of p56lck, a member of the src family of nonreceptor tyrosine protein kinases expressed at high levels in T lymphocytes. The ability of IL-2 to induce p56lck activation was found to be independent of the capacity of p56lck to associate with either CD4 or CD8. Following IL-2 treatment, p56lck was found to undergo serine/threonine phosphorylation modifications that resulted in altered mobility of the lck gene product on polyacrylamide gels. These observations raise the possibility that p56lck participates in IL-2-mediated signal transduction events in T cells.
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PMID:T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck. 200 Apr 5

The T cell antigen receptor complex (TCR) and the interleukin 2 (IL-2) receptor are responsible for signal transduction that results in T lymphocyte activation and proliferation. Stimulation of either the TCR or the IL-2 receptor induces an increase in tyrosine phosphorylation of several cellular proteins indicating that signal transduction by both of these receptors involves the activation of a tyrosine protein kinase. Although the tyrosine protein kinases activated by these receptors have not yet been characterized the receptors themselves are known not to contain a tyrosine protein kinase domain. To determine if these receptors are coupled to the activation of similar or distinct tyrosine protein kinases we examined the patterns and kinetics of tyrosine phosphorylation induced by stimulation of these receptors on a cloned cell line. Hut 78.3 cells co-express the TCR and the p75 IL-2 receptor. These cells were stimulated with either OKT3 antibodies, specific for the TCR, or with IL-2. Signal transduction by these receptors was found to increase the tyrosine phosphorylation of a set of proteins unique to each stimulus. The kinetics of the tyrosine phosphorylation induced by OKT3 antibodies also differed from that induced by IL-2. The OKT3-dependent tyrosine phosphorylation reached maximal levels within 2.5 min and began to decline by 5 min after stimulation. In contrast, the IL-2-induced tyrosine phosphorylation did not achieve maximal levels until 15 min after the addition of IL-2 and the proteins remained phosphorylated even after 60 min of incubation. In addition the tyrosine phosphorylations induced by OKT3 and IL-2 were not affected by prior stimulation with the other agent. These results demonstrate that the TCR and IL-2 receptor are coupled to different signal transduction pathways responsible for the independent activation of distinct tyrosine protein kinases.
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PMID:Stimulation of the antigen and interleukin-2 receptors on T lymphocytes activates distinct tyrosine protein kinases. 235 54

The high-affinity receptor for interleukin-2 (IL-2) is composed of two distinct subunits with molecular weights of 55,000 and 75,000 (p55 and p75). While the presence of the high-affinity receptor requires the simultaneous expression of p55 and p75, these subunits can also be expressed independently, resulting in IL-2 receptors with low and intermediate affinities, respectively. IL-2 can induce proliferation in cells expressing either the intermediate affinity p75 receptor or the p55.p75 high-affinity complex, suggesting that p75 is responsible for signal transduction. We have previously shown that signal transduction by the high-affinity IL-2 receptor involves the activation of a tyrosine protein kinase. In order to evaluate the role of p75 in the activation of this kinase we assessed the ability of IL-2 to induce the activation of a tyrosine protein kinase in the human leukemic cell lines Hut 78 and YT. These cells express p75 as the predominant IL-2 receptor. IL-2-dependent tyrosine phosphorylation was observed in both cell lines and the concentrations of IL-2 needed to stimulate this phosphorylation were similar to that required for binding to the p75 receptor. Antibodies that inhibit binding of IL-2 to p55 had no effect on the IL-2-induced tyrosine phosphorylations in YT cells, while antibodies that block the binding of IL-2 to p75 completely inhibited the phosphorylations. These results demonstrate that the signaling capacity for the IL-2-induced tyrosine phosphorylation resides in the p75 receptor.
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PMID:The 75,000-dalton interleukin-2 receptor transmits a signal for the activation of a tyrosine protein kinase. 251 Nov 97

In rheumatoid arthritis and other inflammatory diseases we and others have found that gamma delta T cells express activation antigens, suggesting that they are involved in the pathogenesis of these disorders. In this study we have stimulated peripheral blood mononuclear cells from normal donors with recombinant interleukin-2 (rIL-2) to see whether such a stimulus alone could activate gamma delta T cells. Short-term exposure (24-96 h) to rIL-2 selectively stimulated the gamma delta but not the alpha beta T cells to express activation antigens (CD69, CD25 and HLA-DR). Long-term culture (2 weeks) in rIL-2-containing medium caused a selective increase in the proportion of the gamma delta T cells and a corresponding reduction of the fraction of alpha beta T cells. Limiting dilution analysis revealed that approximately 1/60 of the gamma delta T cells responded to IL-2 in contrast to only 1/250 of the alpha beta T cells. Comparison of the expression of the IL-2 receptor (IL-2R) alpha and beta chains showed that there was a similar expression of the alpha chain on gamma delta and alpha beta T cells whereas the relative density of the beta chain was more than twice as high on gamma delta T cells. Both the IL-2-induced proliferation of gamma delta T cells and the expression of activation antigens on these cells could be inhibited by an anti-IL-2R beta monoclonal antibody (mAb) but not by an anti-IL-2R alpha mAb. Expression of CD69 on gamma delta T cells was dependent neither on the presence of B cells, monocytes, nor alpha beta T cells. Finally, we found that the IL-2-induced expression of CD69 was inhibited by activation of cAMP-dependent protein kinase and by inhibition of the Src-family of the tyrosine protein kinase, but not by inhibition of protein kinase C or by activation of the CD45 associated tyrosine phosphatase. The ability of gamma delta T cells to be activated by IL-2 is a feature which they have in common with natural killer cells. Moreover, it may be possible that the expression of activation antigens on gamma delta T cells in inflammatory diseases is an epiphenomenon secondary to IL-2 produced by activated alpha beta T cells.
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PMID:Selective activation of resting human gamma delta T lymphocytes by interleukin-2. 837 Mar 91

We investigated activation of mitogen-activated protein (MAP) kinase, also known as microtubule associated protein-2 kinase (MAP-2K), by recombinant interleukin-2 (rIL-2) in phytohaemagglutinin (PHA)-induced peripheral blood lymphoblasts (PBL). MAP-kinase activation has been implicated in growth of lymphocytes and other cell types. Enzyme activity was purified from cell lysates by ion-exchange chromatography and activity measured by the ability to phosphorylate the substrates MAP-2 and myelin basic protein peptide (APRTPGGRR) in vitro. Recombinant IL-2 stimulated a variable (two-to 10-fold) and evanescent MAP-2K response which was dose dependent over the range 0-50 U/ml. In contrast to MAP-kinase activation by the CD3 receptor, activation by the IL-2 receptor (IL-2R) proceeded independently from protein kinase C (PKC) and extracellular-free Ca2+. MAP-kinase activation by CD3 involves an activation cascade which depends on Ca2+ influx and PKC activation. These events culminate in tyrosine phosphorylation and activation of MAP kinase. Recombinant IL-2 induced tyrosine phosphorylation of several intracellular proteins, including a 40,000 MW substrate which co-electrophoresed with ERK-2 on SDS-PAGE. The ERK-2 gene encodes a 41,000 MW MAP-2K and is subject to regulation by a variety of mitogens and growth factors in lymphocytes and non-lymphoid cells. MAP-kinase activation by rIL-2 was abrogated when PHA blasts were pretreated with the tyrosine protein kinase (TPK) inhibitor, methyl-2,5-dihydroxy-cinnamate. Although the TPK, p56lck, has been implicated in the activation of MAP kinase and the function of IL-2R, we found no mobility shift from a 56,000 to a 60,000 MW position as seen during PKC activation. Together these data suggest that tyrosine phosphorylation is critical to IL-2-mediated signal transduction and that MAP kinase is one of the cellular intermediates involved in this pathway.
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PMID:Activation of mitogen-activated protein kinase/ERK-2 in phytohaemagglutin in blasts by recombinant interleukin-2: contrasting features with CD3 activation. 838 29