Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the HER2/neu oncogene in ovarian tumor cells is associated with relative resistance to lymphokine-activated killer (LAK) cell cytotoxicity. Treatment with gamma-interferon (IFN-gamma) (200-2000 units/ml) for 3 days markedly enhanced the sensitivity of HER2/neu-overexpressing ovarian tumor cells to LAK cells but had no effect on the sensitivity of nonexpressing ovarian targets. Increased sensitivity to lysis was associated with an increase in effector-target conjugate formation, the induction of target cell intercellular adhesion molecule 1 (ICAM-1) expression, and the down-regulation of HER2/neu expression. Anti-ICAM-1 antibody blocked the enhanced lysis, indicating that ICAM-1 is important in the increased sensitivity to LAK cells. However, induction of ICAM-1 expression did not correlate well with enhanced sensitivity to lysis; it was maximal after 24 h of exposure to IFN-gamma and still present 24 h after removing IFN-gamma. In contrast, enhanced lysis required 3 days of exposure to IFN-gamma and was reversed within 24 h after removal of IFN-gamma. These data indicate that, although ICAM-1 is necessary, it is not sufficient for the IFN-gamma-induced enhancement of sensitivity to LAK lysis.
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PMID:Interferon-induced increase in sensitivity of ovarian cancer targets to lysis by lymphokine-activated killer cells: selective effects on HER2/neu-overexpressing cells. 134 83

The mutant human cell line 11.1 is unresponsive to interferon alpha. Here we describe the genetic complementation of this mutant and the identification and cloning of the wild-type gene that corrects the defect. Using transfection with genomic DNA in conjunction with a powerful back-selection, we isolated a cosmid that reverts the mutant phenotype of 11.1 cells. The cosmid encodes a single message whose level is greatly reduced in mutant cells. Complementary DNAs were cloned and found to be virtually identical to tyk2, a human mRNA encoding a non-receptor protein tyrosine kinase of previously unknown function. This finding shows that tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes.
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PMID:A protein tyrosine kinase in the interferon alpha/beta signaling pathway. 138 89

In a rapid 51Cr release assay, peripheral blood mononuclear cells from 12 healthy donors did not lyse the hepatitis B virus deoxyribonucleic-acid-transfected human hepatoma cell line 2.2.15, but under the same experimental conditions they did lyse K562 cells. Peripheral blood mononuclear cells from 10 out of 16 patients with chronic active hepatitis B exhibited cytotoxic activity against 2.2.15 cells in the presence of a relatively reduced natural killer cell activity to the K562 cell target. Enhancement of the cytotoxic activity to 2.2.15 cells was statistically significant in the group of patients being treated with leukocyte alpha-interferon. The activity was not influenced by the degree of human leukocyte antigen type matching between effector and target, and was enhanced by depletion of T-cells and by in vitro interferon treatment. These results therefore support the concept of a natural killer-like cell activated by clinical administration of interferon in chronic active hepatitis B patients. This cell effector was lytic for the virus B negative HEP-G2 cells also. However, T-cells purified from a few patients failed to lyse the HEP-G2 while lysing the 2.2.15 target, thus indicating that a preferential recognition of the virus-infected target may be exerted by certain T-lymphocyte subsets. The use of the human leukocyte antigen type defined, highly differentiated, hepatitis B virus releasing 2.2.15 cell line as target for fresh lymphocytes in this cytolytic assay did not disclose cytolytic T-cells in an obvious way. Further manipulation of this system perhaps using T-cell clones may be the next step to exploit the investigative possibilities offered by the availability of the 2.2.15 cell target.
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PMID:Chronic active hepatitis B. Interferon-activated natural killer-like cells against a hepatoma cell line transfected with the hepatitis B virus nucleic acid. 164 27

Alpha interferon (IFN-alpha) is effective in preventing the release of human immunodeficiency virus (HIV) from chronically infected T-lymphocytic (ACH-2) and promonocytic (U1) cell lines stimulated with the phorbol ester phorbol-12-myristate-13 acetate (PMA). In the present study, we observed that together with particle production, shedding of HIV antigen (p24gag) occurs in the T-cell line ACH-2 both constitutively and after stimulation with PMA. IFN-alpha, although effective in suppressing the release of HIV particles, did not inhibit shedding of p24gag into the culture supernatants of either unstimulated or PMA-stimulated cells. These observations may be of relevance in the evaluation of the in vivo efficacy of IFN-alpha treatment of HIV-infected individuals as determined by levels of p24 antigen in plasma.
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PMID:Alpha interferon suppresses virion but not soluble human immunodeficiency virus antigen production in chronically infected T-lymphocytic cells. 171 Feb 93

Two cultures chronically infected with distemper virus (HEP-2 and L-41) were obtained. The cultures produced a small-plaque cell-associated virus and a virus-specific antigen which was demonstrated by the fluorescence antibody technique in 40%-60% of the cells. The chronically infected cells produced interferon as judged by their resistance to superinfections with heterologous viruses. The virus-carrier state was characterized by temperature sensitivity.
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PMID:[The persistence of the distemper virus in continuous human cells]. 171 29

The bacterial superantigen staphylococcal enterotoxin (SE) A (SEA) directs cytotoxic T lymphocytes (CTLs) expressing particular sequences of the T-cell receptor (TCR) beta chain to lyse tumor cells expressing major histocompatibility complex (MHC) class II molecules, which serve as receptors for SEs. We now report that chemical conjugates of SEA and the colon carcinoma-reactive monoclonal antibodies (mAbs) C215 or C242 mediate T cell-dependent destruction of colon carcinoma cells lacking MHC class II molecules. SEA was covalently linked to the mAbs C215 and C242 via a PEG-based hydrophilic spacer. The C215-SEA conjugate targeted CD4+ as well as CD8+ CTLs to lyse a panel of colon carcinoma cells lacking MHC class II molecules. T-cell recognition of mAb-SEA conjugates was SEA specific, since SEB-selective T-cell lines with potent cytotoxic activity towards Raji cells coated with SEB did not respond to the C215-SEA conjugate. Unconjugated SEA did not induce T-cell lysis of MHC class II- colon carcinoma cells but efficiently directed CTLs against MHC class II+ Raji cells and certain interferon-treated MHC class II+ colon carcinoma cells. These results suggest that SEA-mAb conjugates retain the SEA-related selectivity for certain TCR beta-chain variable region (V beta) sequences but, in contrast to unconjugated SEA, mediate the TCR interaction in a MHC class II-independent manner. The cytotoxic activity mediated by C215-SEA and C242-SEA conjugates was blocked by excess of C215 mAb and C242 mAb, respectively, showing that the specificity in the targeting of mAb-SEA conjugates is defined by the antigen reactivity of the mAb. These results demonstrate that bacterial superantigens may be successfully conjugated to mAb with preserved T cell-activating capacity. The circumvention of MHC class II binding of SEs by conjugation to mAb suggests that such conjugates may find general application as antitumor agents, taking advantage of the extreme T cell-activating potency of superantigens.
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PMID:Monoclonal antibody-targeted superantigens: a different class of anti-tumor agents. 192 93

Human CD4+ T cells differ in their expression of the leucocyte common antigen. Antibodies detecting certain forms (CD45RA and CD45RO) of this antigen have been used to identify and isolate subpopulations of the CD4+ T cells. These isolated subsets have been shown to have different abilities concerning lymphokine production and provision of help to B cells for Ig production. When these T-cell subsets were activated in vitro with polyclonal activators, the production. When these T-cell subsets were activated in vitro with polyclonal activators, the CD45RA+ cells lost this marker and gained the expression of CD45RO. This was true for all mitogens used in this report, i.e. accessory cell-dependent stimulation with SEA and accessory cell-independent activation with PMA or PHA. A correlation between proliferation and differentiation was observed, but this was probably not causative as stimulation with PMA in the absence of DNA synthesis resulted in the acquisition of CD45RO and loss of the CD45RA antigen. Moreover, cells proliferating vigorously for long periods of time expressed both markers at significant levels, which suggests that proliferation did not automatically result in complete loss of the CD45RA marker. The phenotypical differentiation was associated with a functional differentiation which induced the stimulated cells' ability to act as helper cells for Ig production and to produce gamma interferon (IFN-gamma). The results obtained in this study support the contention that the CD45RA+ cells are precursors of the CD45RO+ cells and that the two subsets represent different maturational stages of the same lineage.
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PMID:Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation. 214 7

The interferons (IFNs) have been shown to be antagonistic to the growth stimulatory effects of mitogens on cultured cells. A report of the interactions of IFN-beta and platelet-derived growth factor on BALB/c-3T3 mouse cells established that IFN itself induced the secretion of a limited number of proteins from this cell line. The present work was undertaken to determine if other murine cell lines treated with homologous IFN-beta also secreted new or additional protein(s) in response to this agent and if this response correlated with other phenotypic properties of the cells. The cell lines examined included L929 cells and two derivatives of this line (GM347 and WDIFN), CAK-TK-, Swiss-3T3, and BALB/c-3T3. Each line was exposed to [35S]methionine in the absence and in the presence of IFN-beta, the supernatant fluids collected, and the radioactive, secreted proteins examined by fluorography after electrophoresis through SDS-containing polyacrylamide gels. Two cell lines (GM347 and Swiss-3T3) did not appear to secrete new or additional proteins after IFN treatment. However, four lines (L929, WDIFN, CAK-TK-, and BALB/c-3T3) did secrete new or additional proteins in response to IFN. Thus IFN-induced secretion of protein appeared to be a common but not universal phenomenon. In addition, although the number and apparent size(s) of the IFN-induced, secreted proteins were different in these various lines, one protein (Mr = 89-90,000) appeared to be secreted by each of them. In this respect it was unique. Moreover the IFN-induced secretion of protein did not appear to correlate with the antiviral or antiproliferative effects of IFN.
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PMID:Effect of interferon on secretion of proteins by various murine cell lines. 245 71

After a single intraperitoneal inoculation of C57BL/6 mice with enterotoxin A of Staphylococcus aureus (SEA) the activity of natural killers (NK) increases and phase change of interferon production by spleen cells upon reinduction in vitro occurs. Multiple daily inoculations of mice with SEA maintain the activity of splenic NK at a similar high level. With an adequate control (multiple administration of the medium) NK activity was maintained at the same high level. Interferon production by spleen cells of mice which were multiply inoculated with the medium upon reinduction in vitro was the same as in the control animals, whereas after multiple inoculations of mice with SEA, spleen cells in vitro produced lower amounts of interferon.
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PMID:[Interferon production and natural killer activity induced by staphylococcal enterotoxin in mouse spleen cells]. 245 49

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.
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PMID:[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon]. 261 34


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