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)

The early events of signal transduction associated with interleukin-2 (IL-2) binding to its receptor were examined using a human IL-2 dependent T-cell line, Kit225. Cell cycle analysis showed that 90% of Kit225 cells were in the G0/G1 phase after a 72-hr incubation in the absence of exogenous IL-2. At this point, stimulation of the cells with IL-2 resulted in the rapid initiation of RNA and DNA synthesis by 9 and 20 hr, respectively. Within 5 min after addition of IL-2, rapid activation of tyrosine and ribosomal S6 kinases was detected. Addition of IL-2 also increased mRNA levels for c-fos, c-myc, IL-2 receptor alpha, and IL-2 receptor beta chain. These events increased in the absence of detectable changes in free cytosolic [Ca2+]i, inositol phosphate metabolism, or the activity of several kinases including cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase, or protein kinase C. These findings demonstrate that the signals triggered by IL-2 binding to its receptors are quickly transduced into the nucleus with increased mRNA transcription of activation-associated genes. Furthermore, the data indicate that tyrosine and ribosomal S6 kinases may be important for IL-2-induced cell growth.
 ...
PMID:Signal transduction by interleukin 2 in human T cells: activation of tyrosine and ribosomal S6 kinases and cell-cycle regulatory genes. 131 23

A human leukemia cell line, JK-T1, was established from the bone marrow of a 10-year-old boy with T-cell acute lymphoblastic leukemia. The origin of the leukemic cell line, JK-T1, was demonstrated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. Karyotypic analysis revealed 46,XY,del(6)(q?),t(8;14)(q24;q13),der(9)t(9;?)(q34;?). In JK-T1, neither rearrangement nor amplification of the c-myc gene was observed apparently because the breakpoint of chromosome 14 was not q11 but q13. JK-T1 was independent of interleukin 2 (IL-2) because of little production of IL-2, little IL-2 receptor (CD25) on the surface, and no response to exogenous IL-2. JK-T1 had lymphocyte function associated antigen-1 (LFA-1) (CD11a, CD18) on its surface and could adhere to the hematologic stromal layer. These characteristics of JK-T1 cell line are considered to be useful not only for evaluating the role of t(8;14) but also in studying the adhesion molecules of leukemia.
 ...
PMID:Establishment and characteristics of a T-cell acute lymphoblastic leukemia cell line, JK-T1, with a chromosomal translocation between 8q24 and 14q13. 133 81

We investigated the possible role of tumor necrosis factor-alpha (TNF-alpha) in the interleukin-2 (IL-2)-dependent generation of natural killer (NK) cells from bone marrow precursors. TNF-alpha synergistically augmented both cytotoxic activity against NK-sensitive targets and cell number at the end of the 7-day incubation period. After this time, NK activity was not induced by TNF-alpha in the absence of IL-2. The cytotoxic cells generated by IL-2 + TNF-alpha had the phenotype of mature NK cells, including expression of NK-1.1, asialo-GM1, Ly-5, LFA-1 and Thy-1. TNF-alpha was also able to up-regulate the mRNA expression for the IL-2 receptor alpha-chain (P55) as well as the mRNA expression of c-myc protooncogene. Blocking studies with monoclonal antibodies against the alpha-chain P55 of the IL-2 receptor confirmed the functional role ascribed to IL-2 in the in vitro generation of NK cells from bone marrow cultures. Additional proliferation studies demonstrated that the up-regulation of c-myc protooncogene was associated with an increased uptake of thymidine. These data indicate that the TNF-alpha-induced increase of IL-2-dependent NK cell generation from bone marrow precursors was associated with an augmented proliferation and an up-regulation of mRNA expression for IL-2 receptor and c-myc protooncogene.
 ...
PMID:Effect of recombinant murine tumor necrosis factor on the generation of natural killer cells in bone marrow cultures. 149 22

Stimulation via cytokine receptors such as IL-2 and IL-3 receptors, but not by the EGF receptor (EGFR), induces cells of the BAF-B03 hematopoietic cell line to transit the cell cycle. We demonstrate that the IL-2 receptor beta chain (IL-2R beta) is linked to at least two intracellular signaling pathways. One pathway may involve a protein tyrosine kinase of the src family, which leads to the induction of the c-jun and c-fos genes, among others. A second pathway, involving an as yet unknown mechanism, leads to c-myc gene induction. Stimulation of the EGFR, expressed following transfection of an appropriate recombinant construct, can activate the former, but not the latter, pathway in this cell line and cause the cells to enter S phase but not progress further. This deficiency can be rescued by ectopic expression of the c-myc gene, indicating a novel role for this proto-oncogene in the S to G2/M transition of the cell cycle.
 ...
PMID:IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc. 153 27

We demonstrate that stimulation with interleukin (IL)-1 and IL-6 prepares high-density B cells to enter the S phase more promptly in response to subsequent stimulation with anti-mu F(ab')2. The stimulatory effect of IL-1 and IL-6 is compared to the one described for IL-4. In contrast to IL-4, preculture in IL-1 and IL-6 does not induce an increase in cell volume or in expression of class II major histocompatibility complex antigens on resting B cells. Similarly, the expression of the p55 subunit of the IL-2 receptor and of the transferrin receptor was not detected on resting B cells stimulated with IL-1 and IL-6. However, the stimulatory effect of IL-1 and IL-6 is correlated with an increased expression of c-myc proto-oncogene mRNA in resting murine B cells.
 ...
PMID:Interleukin-1 and interleukin-6 synergize in preparing resting murine B cells to respond to anti-mu: correlation with c-myc expression. 155 52

Interleukin-2 (IL-2) plays a central role in the immune system by regulating the proliferation and differentiation of T lymphocytes. However, the molecular mechanism of the signal transduction through the IL-2 receptor is poorly understood. We have studied the role of phosphatidic acid (PA) on IL-2 signal transduction using cloned T lymphocytes. IL-2 stimulated a transient increase in the PA concentration in resting CTLL-2 cells prelabeled with [3H]palmitic acid. This effect was detected as early as 1 min after IL-2 addition and peaked at 5 min. IL-2 similarly increased phospholipase D activity in intact CTLL-2 cells, as inferred by phosphatidylethanol production. By contrast, IL-2 did not affect [3H]palmitic acid-labeled diacylglycerol levels. Furthermore, exogenous addition of several natural or synthetic PA to T cells mimicked IL-2 activity. Thus, PA were able to induce DNA synthesis on CTLL-2 cells, although this effect was only 10%-20% of that observed with IL-2. PA showed a synergistic effect with low doses of IL-2. In addition, PA was able to induce c-myc RNA transcription in CTLL-2 cells as well as IL-2 receptor (CD25) expression on the cell membrane with equal potency as saturating doses of IL-2. It is likely that IL-2-induced PA accumulation is a consequence of phospholipase D activation. This hypothesis is further supported by the fact that the addition of exogenous phospholipase D but not phosphatidylinositol-specific phospholipase C also reproduced the IL-2 or PA effects mentioned above. In summary, our results suggest a role of phospholipase D activation and PA formation as second messengers of IL-2 activity.
 ...
PMID:Regulation of interleukin-2 responses by phosphatidic acid. 162 28

Measles virus (MV) inhibits lymphocyte function in patients, as well as in cells infected in vitro. The proliferation of phytohemagglutinin-stimulated T lymphocytes is suppressed by in vitro MV infection, as shown by the diminished incorporation of [3H]thymidine into DNA and the reduced frequency of cells in the S phase of the cell cycle, as compared with mock-infected cells. MV infection itself, however, does not completely block DNA synthesis in infected cells, because infected T cells expressing MV antigens on the cell surface, isolated by fluorescence-activated cell sorter, could still proliferate. Northern blot analysis indicated that the expression of genes induced during T cell activation, such as those encoding interleukin 2 (IL-2), c-myc, IL-2 receptor, IL-6, c-myb, and cdc-2, was not significantly suppressed in MV-infected cells, suggesting that MV does not interfere with the T cell activation process. When anti-MV serum or carbobenzoxy-D-Phe-L-Phe-Gly, a synthetic oligopeptide known to inhibit MV-induced fusion, was added 24 hr after infection, the inhibition of T cell proliferation was reversed in a dose-dependent manner. From these results we propose a model for the inhibition of T cell proliferation by MV; MV glycoproteins expressed on the cell surface of infected cells interact with the MV receptor or other molecules on the cell membrane of adjacent T cells, which in turn affects the proliferation of those T cells.
 ...
PMID:Measles virus inhibits mitogen-induced T cell proliferation but does not directly perturb the T cell activation process inside the cell. 173 30

The immunosuppressive drug, mizoribine, has been used to prevent rejection of organ allografts in humans and in animal models. Based on studies in cell lines, mizoribine has been postulated to be an inhibitor of inosine monophosphate (IMP) dehydrogenase (EC1.2.1.14), a pivotal enzyme in the formation of guanine ribonucleotides from IMP. To further characterize the mechanism of action of this drug, we studied the effect of mizoribine on human peripheral blood T cells stimulated with alloantigen, anti-CD3 MAb, or pharmacologic mitogens. Mizoribine (1-50 micrograms/ml) was able to inhibit T cell proliferation by 10-100% in a dose-dependent fashion to all stimuli tested. Measurements of purine ribonucleotide pools by HPLC showed that mizoribine led to a decrease in intracellular GTP levels, and that repletion of GTP reversed its antiproliferative effects. We also examined sequential events occurring after T cell stimulation. Early events in T cell activation, as assessed by steady-state mRNA levels of c-myc, IL-2, c-myb, histone, and cdc2 kinase, as well as surface IL-2 receptor expression, were unaffected. However, cell cycle analysis revealed decreased numbers of cells in S, G2, and M phases, and showed that the G1/S block was reversed with GTP repletion. These data indicate that mizoribine has an effect on T cell proliferation by a mechanism distinct from that of cyclosporine or corticosteroids, and therefore may be useful in combination immunosuppressive regimens.
 ...
PMID:Guanine ribonucleotide depletion inhibits T cell activation. Mechanism of action of the immunosuppressive drug mizoribine. 199 2

The above sections have provided numerous facts, many of which are conflicting, regarding the changes that occur with increasing age in T lymphocytes. Although it is impossible to state with absolute certainty the alterations that are responsible for decreased proliferation of lymphocytes from elderly subjects, the following summarizes the current status of the data: 1. The interaction of T lymphocytes with foreign stimuli appears to be generally intact. 2. Changes in numbers of CD3+, CD4+, or CD8+ cells before interaction with foreign stimuli or in the density of these markers or of mitogen receptors on the surface of aged T cells have not been consistently observed. When reported to occur, the changes are not sufficient to account for the significant decrease in T-cell proliferation that occurs with increasing age. 3. A defect in the ability of the membrane interaction with foreign stimulus to signal subsequent internal events may occur, because stimulation with phorbol esters and calcium ionophore can result in increased proliferation in some elderly subjects. 4. Decreased accumulation of cytosolic calcium after stimulation of elderly T cells occurs in mice and may be a major component of the defective activation system. This defect appears to be most apparent in the "memory" T cells (T cells expressing high levels of Pgp-1), which increase in number with increasing age. Decreases in Ca++ accumulation have not been observed in humans, but this may be due to different stimuli used. Further, investigation of an increase in "memory" T cells and of their inability to mobilize Ca++ has not been done in humans and rats. 5. Decreases in mRNA for c-myc, IL-2 receptor, and IL-2 have been reported in some, but not all, species. Whether these decreases are the result of decreases in Ca++ mobilization or are independent events in unknown. 6. Decreases in membrane expression of the activation marker RL388 and of TfR have been reported. 7. Lymphokines: a. Decreases in IL-2 production occur in mice and humans, but not in rats. In individuals with decreased IL-2 production, addition of exogenous IL-2 totally restores proliferative ability in only some individuals. Changes in IL-2R expression (number or affinity) may be an additional defect. b. Decreases in IFN-gamma occur in humans, but not in mice or rats. c. No change in IL-1 occurs in any species. Genotypic effects must be considered when evaluating the preceding observations. The heterogeneity among individuals, even within an inbred strain, cannot be discounted.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:T-cell function in aging: mechanisms of decline. 210 13

Total mRNA was extracted from activated T lymphocytes and Jurkat cells with and without heat shock, and then used for alpha-32P-labeled 1st strand cDNA synthesis with reverse transcriptase. DNA restriction fragments or cloned vectors of five oncogenes (abl, myc, myb, fos, Ki-ras) and of IL-2, IL-2 receptor, T-cell receptor beta-chain and transferrin receptor were dotted onto nitrocellulose filters. Hybridization results showed that the expression of c-myc and TfR mRNA was much lower in heat-shocked cells than in their normal counterparts. However IL-2 and Ki-ras mRNA increased after heat shock. Possible explanations for the results are discussed.
 ...
PMID:[The effect of heat shock on mRNA expression in human T lymphocytes]. 215 Dec 59


1 2 3 4 5 Next >>