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)

Murine thymocytes were stimulated with the protein kinase C activating agents Phorbol-12-myristate-13-acetate (PMA) or a more physiological membrane permeant diacylglycerol (dioctanoyl-sn-glycerol, DiC8) in the presence or absence of exogenous lymphokines (rIL-1 beta, rIL-2). Whereas PMA directly induced reactivity to rIL-2, DiC8 did not but had to synergize with the calcium ionophore Ionomycin. Expression of the p55 chain of the IL-2 receptor behaved similarly. In the absence of exogenous rIL-2, thymocytes proliferated in response to a combination of Ionomycin and PMA; however, replacing PMA by a single addition of DiC8 did not result in proliferation. Stimulation with Ionomycin plus repeated addition of DiC8 induced a low level of thymocyte proliferation and further addition of rIL-1 beta resulted in a significant increase. Purified immature (L3T4-Lyt2-) thymocytes behaved similarly, but showed an increased sensitivity to rIL-1 beta. Taken together, the data support the idea that PMA and the more physiological diacylglycerols do not possess totally equivalent activities in lymphocyte stimulation.
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PMID:Distinct effects of phorbol esters and exogenous diacylglycerols in the induction of murine thymocyte proliferation. 156 51

Recently, we have shown that soluble factors released by human lymphocytes after lectin stimulation could increase the contractile tension of rat atria "in vitro" and that interleukin-2 (IL-2) could be part of this reaction. The effect of IL-2 was potentiated by the Ca2+ ionophore A23187 or free arachidonic acid (AA). In this study we demonstrate that the action of IL-2 can be prevented by pre-incubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-p55), suggesting that binding to the IL-2 receptor is necessary for the induction of the biologic effect. In the presence of A23187 or AA, the effect of the synthetic diacylglyceride oleoyl-acetyl-glycerol (OAG) was similar to that of IL-2. Elimination of phospholipase C activity by pre-incubation of the atria with 2-nitro-carboxyphenyl,N,N'-diphenylcarbamate (NCDC) abrogated the effects of IL-2 in the presence of A23187 or AA, but was ineffective when OAG + A23187 or OAG + AA was used. Inhibition of atrial phospholipase A2 activity with p-bromo-phenacylbromide (BPB) blocked the response of atria to either IL-2 + A23187 or OAG + A23187 but was not effective when AA was used as second signal (IL-2 + AA or OAG + AA). Both the OAG and the IL-2 positive inotropic effects could be prevented by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H7) but were poorly inhibited by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), an inhibitor of the cyclic nucleotide-dependent protein kinases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Positive inotropic effect of interleukin-2. Role of phospholipases and protein kinase C. 178 63

An increase in the isometric developed tension (IDT) of isolated rat atria was observed shortly after the addition of human interleukin 2 (IL-2) to the organ preparation with subthreshold concentrations of either arachidonate (AA, 1.98 X 10(-6)M) or the calcium ionophore A 23187 (1.9 X 10(-6)M). Both natural purified IL-2 (nIL-2) and yeast recombinant IL-2 (rIL-2) were active in this experimental system. It was determined that this lymphokine was active at 2 X 10(-11)M, considering as a reference the specific activity of rIL-2. Anti-IL-2 monoclonal antibody (anti-IL-2 MAb) abolished this reaction. Inhibition of atrial phospholipase C activity by nitrocarboxyphenyl N,N-diphenylcarbamate (NCDC, 5 X 10(-6)M) prevented the development of the inotropic positive effect of IL-2 in the presence of either AA or A 23187. The synthetic diacylglyceride 1-oleoyl, 2-acetyl-glycerol (OAG) replaced the IL-2 as stimulatory signal but NCDC had no effect on the reaction. The results suggest that IL-2 can alter the physiologic behaviour of the heart and that its mechanism of action is probably similar to the one proposed for other IL-2 targets (IL-2 receptor-positive T lymphocytes, T cell lines).
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PMID:Interleukin 2 stimulates heart contractility in the presence of exogenous arachidonate or the calcium ionophore A 23187. 312 71

The activation of protein kinase C (PKC) is believed to result from the translocation of inactive cytosolic enzyme to the lipid environment of membranes. However, by using a novel method for measuring PKC activity directly in isolated membranes, we have previously shown that a significant proportion of the PKC present in a variety of cells associates with membranes in an inactive state, and that this pool of inactive PKC can be stimulated specifically in cells in the absence of translocation. IL-2 did not stimulate the translocation of PKC to membranes in the IL-2-dependent mouse T cell line, CTLL-2. Nevertheless, a transient, two approximately threefold increase in membrane PKC activity was observed within 10 min of IL-2 addition to these cells. This increase was entirely caused by the activation of a pool of inactive membrane PKC previously associated with the membrane. The inhibition of PKC activity by the specific inhibitors bisindolylmaleimide (BIS) and 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG) blocked the ability of IL-2 to suppress the onset of apoptosis in IL-2 and serum-deprived CTLL-2 cells. The inhibition of this important function of IL-2 was most pronounced when the PKC inhibitors were added to the medium within 2 h of stimulating the cells with IL-2. The results suggest that transient activation of inactive membrane PKC is linked to the IL-2 receptor signaling, and may be an important step in the mechanism(s) by which the cytokine suppresses cell death in T lymphocytes.
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PMID:Evidence that the activation of an inactive pool of membrane-associated protein kinase C is linked to the IL-2-dependent survival of T lymphocytes. 804 29