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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have devised an immunological procedure to separate cells on the basis of expression of mouse mammary tumor virus (MMTV) gene products. Plastic petri dishes coated with specific antibodies against MMTV proteins bind cells with an efficiency that correlates with the level of MMTV gene expression. Glucocorticoid-sensitive mouse thymoma cell line W7 was infected with MMTV. Clones from the infected population retain the relatively slow cytolytic glucocorticoid response and, in addition, exhibit a rapid induction of MMTV-specific RNA and proteins. By combining our immunological selection with the selection for resistance to hormone-mediated cytolysis, we have isolated variant cells which are resistant to the cytotoxic effect of glucocorticoids but which retain the induction of viral gene products and must therefore have a functional glucocorticoid receptor protein.
Mol Cell Biol 1983 Jul
PMID:Immunological selection of variant mouse lymphoid cells with altered glucocorticoid responsiveness. 631 Mar 72

The LSTRA murine thymoma cell line contains an elevated level of tyrosine protein kinase activity. When a microsomal preparation from these cells is incubated in vitro with ATP, the principal tyrosine protein kinase substrate is a 56,000-dalton protein, p56. We have found that an activity phosphorylating p56 on tyrosine can also be detected at low levels in microsomes from most, but not all, T lymphoma cell lines and from normal thymic tissue. Only 1 of 30 other lymphoma cell lines was found to contain an elevated level of such a tyrosine protein kinase. An activity that phosphorylated p56 in vitro was not detectable in the cells of other hematopoietic lineages. Anti-peptide antibodies reactive with the site of in vitro tyrosine phosphorylation of p56 allowed us to determine that the apparent abundance of the p56 polypeptide parallels closely the level of the tyrosine protein kinase activity in the cell lines examined. This suggests that p56 is the protein kinase responsible for the elevated tyrosine protein kinase activity in LSTRA cells and that the phosphorylation of p56 observed in vitro results from autophosphorylation. Two-dimensional tryptic peptide mapping revealed that p56 is distinct from the proteins encoded by the cellular genes which are the progenitors of retroviral tyrosine protein kinases, src, yes, fgr, abl, fes, and ros. Additionally, none of these proto-oncogenes was found to be transcribed at elevated levels in LSTRA or Thy19 cells. Like the catalytic subunit of the cyclic AMP-dependent protein kinase, the cellular and viral forms of p60src, and the protein phosphatase calcineurin B, p56 contains covalently bound fatty acid.
Mol Cell Biol 1984 Dec
PMID:Characterization of the protein apparently responsible for the elevated tyrosine protein kinase activity in LSTRA cells. 654 43

The mouse thymoma-derived cell line W7 is sensitive to the cytolytic action of glucocorticoids. We have isolated a novel class of cell variant that apparently overcomes its inherent sensitivity to glucocorticoids by reversibly down-regulating the level of glucocorticoid receptors. This phenotype is stable during subcloning in the presence and in the absence of glucocorticoids and is dominant in somatic cell hybrids with wild-type cells. Fusion of this variant with wild-type cells produces hybrids that down-regulate and are less sensitive to glucocorticoids than hybrids of receptor-negative and wild-type cells. This is the first demonstration of a phenotypic change which correlates with down-regulation of the glucocorticoid receptor.
Mol Cell Biol 1984 Mar
PMID:Down-regulation of glucocorticoid receptors in mouse lymphoma cell variants. 654 69

Approximately 60% of mice treated with split-dose radiation develop leukemias that disseminate widely through the body, whereas 40% of the treated mice incur leukemias that are contained entirely within the thymus. We studied the status of p53 in non-cultured samples of thymic leukemias and in cell lines established from these leukemias. In those mice with disseminated disease, primary samples were also obtained from visceral leukemic organs, and cell lines were established from these leukemic organs for further study. Using single-strand conformation polymorphism (SSCP), nucleic acid sequencing, and immunochemical analysis, we found that mutation of both p53 alleles occurred in leukemic cell lines developed from nine of 10 disseminated leukemias; mutation of one p53 allele with the other remaining wild-type occurred in one disseminated leukemia. A p53 mutation unique for each mouse was found in all cell lines established from the different leukemic organs of each mouse. The same mutation was also found in the non-cultured leukemic tissues of each mouse, indicating that the mutations originated in vivo and were clonal. Seven of seven non-disseminating thymomas possessed wild-type p53 only. Hence, in vivo dissemination and tissue invasiveness were associated with the loss of wild-type p53 by mutation of both alleles or by mutation and loss of heterozygosity, as revealed by studies of cell lines established from them. The selective in vivo dissemination of leukemia cells possessing p53 mutations had a parallel in vitro. Leukemia cell lines from mice harboring disseminating leukemia were established more readily (success rate greater than 80%) than lines from mice harboring thymic nondisseminating leukemia (success rate less than 10%). Additionally, while mice with disseminating leukemia harbored a mixture of wild-type and mutant p53-encoding thymoma cells, only cell lines possessing mutant p53 became established in culture. Mutations found in thymoma cell lines were always detectable by SSCP and sequencing of DNA extracted from non-cultured thymoma tissue. However, in non-cultured leukemic tissue of visceral organs, the clonal p53 mutations found in cell lines established from them were often not detectable by SSCP or sequencing but were detectable by immunochemical analysis or polymerase chain reaction amplification. This indicates an unexpected degree of masking of mutant genes by wild-type genes present in the leukemic tissue. Masking was evident even in leukemic organs that were grossly larger than normal organs. Hence, routine screening of leukemic tissue by SSCP and sequencing may result in a highly significant underestimation of the incidence of p53 mutations.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Carcinog 1995 Jun
PMID:Dissemination and tissue invasiveness in murine acute leukemia associated with acquisition of p53 mutation and loss of wild-type p53. 760 79

We have examined the regulation of the AP-1 DNA transcription complex during T cell activation in response to interleukin 1 (IL-1) and phorbol ester (TPA) treatment of the IL-1 responsive murine thymoma T cell line, EL4 6.1 C 10. IL-1 synergistically enhances the stimulatory effect of TPA on AP-1-mediated gene expression in this cell line. To elucidate the mechanism(s) by which IL-1 enhances AP-1-mediated gene expression, we examined the effect of IL-1 on the synthesis and turnover of Jun B, the member of the jun gene family that is present in AP-1 complexes in EL4 cells. We found that IL-1 + TPA-treated cells contain significantly higher Jun B protein levels than cells treated with TPA alone. IL-1 promotes the prolonged accumulation of Jun B, whereas the cellular content of Jun B decreases dramatically after 6 hr in cells treated with only TPA. IL-1 enhancement of Jun B protein levels is not the result of a change in the turnover rate of the Jun B protein, but rather results from the maintenance of sufficient jun B mRNA to support continued accumulation of newly synthesized protein. In addition to Jun B, we found that the T cell AP-1 complex contains the Fra-1 protein, a member of the fos gene family. Although IL-1 dramatically increases Jun B accumulation, it does not enhance TPA-induced Fra-1 protein levels in EL4 cells. Thus, the stimulation of AP-1-mediated gene expression by IL-1 in EL4 cells is due to the promotion of Jun B protein accumulation that, in turn, facilitates Jun B heterodimerization with TPA-induced Fra-1 protein, thereby forming an active AP-1 complex.
Mol Immunol 1995 Aug
PMID:Interleukin 1 activation of the AP-1 transcription complex in murine T cells is regulated at the level of Jun B protein accumulation. 767 40

Immunosuppressive factor (ISFnp) which inhibits proliferation and viability of thymoma EL-4 cells was isolated from mouse liver. The testing procedure based on the biotransformation of MTT-tetrazolium by mitochondrial enzymes of viable cells allowed us to purify this factor as individual peak of protein, that allowed to obtain polyclonal rabbit antibodies to this factor. By the methods of double immunodiffusion, gel-filtration and SDS-PAGE with subsequent immunoblotting we shown that this factor specifically localized in liver and consists two subunits of 40 and 42 kDa which form dimers with apparent M(r) about 70-80 kDa. This factor induced olygonucleosomal DNA cleavage in EL-4 cells in vitro similar to dexamethasone-induced DNA-degradation in thymocytes. This cleavage preceded to lysis of EL-4 cells assessed by 51Cr-release, that strongly suggested an involvement of apoptosis in cell death mechanism. ISFnp strongly inhibited blast-transformation and proliferation in MLC-responses to mutant MHC class 2 molecule. This effect was not due to deletion of allo-reactive clones, because removing of this factor from MLC cultures treated with one for 4 days resulted in blast-transformation without any reduction of the number of viable cells as well as their capacity for secondary responses to the same antigen as compared with control cultures.
Mol Biol (Mosk)
PMID:[Isolation, study of activity, and characteristics of an immunosuppressive liver factor causing apoptosis of EL-4 thymoma cells in vitro]. 772 57

The experimental system to scrutinize the in vitro proliferation of thymus epithelial cells (TECs) was established on the basis of enhancing their mitotic index and DNA synthetic activity. The TEC line, TAD3 derived from lymphocyte-dominant thymoma, was used as the cell material. Growth hormone (GH) induced a significant proliferation of the cultured cell line in the preconfluent state. The optimal concentration of and the duration of the incubation with GH, in this system, were 50 ng/ml and 18 hrs., respectively. Furthermore, insulin-like growth factor-I (IGF-I), the mediator of somatotropic action of GH, also enhanced the DNA synthetic activity of the cultured cells in the preconfluent state. The authors recently found that the TECs, stimulated with GH, released significantly more IGF-I than the cells without GH. It is possible that there are two systems in the TEC proliferation, namely, direct induction by GH itself and indirect induction by IGF-I released from the GH-stimulated TECs. The data showing that GH could directly or indirectly induce proliferation of TECs might possibly be related to the formation of epithelial thymic rudiment in the fetal stage.
Cell Mol Biol (Noisy-le-grand) 1994 Dec
PMID:The in vitro proliferation of thymus epithelial cells stimulated with growth hormone and insulin-like growth factor-I. 787 85

The T cell protein tyrosine kinase p56lck is implicated in thymic development and mitogenic activation of T lymphocytes, and is itself regulated by reversible tyrosine phosphorylation. When phenylarsine oxide (PAO), a membrane-permeable inhibitor of phosphotyrosine phosphatases, was added to Jurkat T leukemia or LSTRA thymoma cells, the phosphate content of p56lck increased rapidly. The sites of increased phosphorylation were mapped to Tyr-192, Tyr-394 and Tyr-505. Hyperphosphorylated p56lck displayed retarded mobility on SDS gels, unaltered or marginally increased cytoskeletal association, and its catalytic activity changed in a biphasic manner; during the first 10-20 min of PAO-treatment the activity increased and then it declined to very low values within 1-2 hr. Our data suggest that p56lck contains both positive and negative regulatory sites which are constantly dephosphorylated at an unexpectedly high rate by cellular phosphotyrosine phosphatases.
Mol Immunol 1994 Dec
PMID:Induction of hyperphosphorylation and activation of the p56lck protein tyrosine kinase by phenylarsine oxide, a phosphotyrosine phosphatase inhibitor. 799 41

The genetic components required for glucocorticoid induction of apoptosis were studied by using somatic cell hybridization. Intertypic whole-cell hybrids were generated by crossing the glucocorticoid-resistant rat liver cell line Fado-2 with the glucocorticoid-sensitive mouse thymoma cell line BW5147.3. Morphological and biochemical criteria were used to assess sensitivity or resistance to glucocorticoid-induced cell death. Both phenotypes were observed, and all of the hybrids retained a functional glucocorticoid receptor as judged by their abilities to induce the metallothionein gene in response to dexamethasone (Dex). Sensitivity to apoptosis did not correlate with morphological phenotype in that not all suspension cells were sensitive. The effect of glucocorticoids on the expression of apoptosis-linked genes was analyzed in a subset of Dex-sensitive and Dex-resistant hybrids. p53 and c-myc mRNAs were present in parental cells as well as sensitive and resistant hybrid cells, and their levels were not affected by glucocorticoid treatment. bcl-2 expression was restricted to the thymoma cell line and was also not affected by glucocorticoids. We did not detect any bcl-2 mRNA in the hepatoma cell line and the hybrids, suggesting that, as with most tissue-specific genes, bcl-2 is regulated in trans. Furthermore, while the majority of hybrids analyzed retained a full complement of mouse chromosomes, sensitive hybrids were missing some rat chromosomes (preferentially chromosomes 16 and 19), indicating that apoptosis is subject to trans repression. Resistant cells thus appear to repress the activity or synthesis of a nuclear factor that interacts with a glucocorticoid-dependent gene(s) to activate the cell death pathway.
Mol Cell Biol 1994 Sep
PMID:Evidence for trans regulation of apoptosis in intertypic somatic cell hybrids. 806 45

The effect of a short-term energy deprivation (ischemia) on thermoresistance and heat-shock protein (HSP) synthesis in murine ascites EL-4 thymoma cells was studied in vitro. The incubation of the cells in glucose-free medium with rotenone (respiratory inhibitor) for 10 min caused rapid ATP depletion (to 9% of the initial level). After recovery, the synthesis of HSP70 and HSP90 was stimulated in the cells and they became greatly more resistant to hyperthermia than the control cells. The simultaneous rotenone and thermal treatment significantly decreased cell viability. The transition of HSP70 to Triton X-100-insoluble cell fraction was found in the ATP-depleted cells as well as in the heat-shocked cells, and 1 mM ATP fully reversed such insolubilization when it was added in Triton extraction buffer. The data obtained reveal that transient ATP depletion per se is sufficient to result in the HSP70 insolubilization, thus being conducive to induction of HSP synthesis and thermotolerance in the cells which recovered after energy deprivation. A novel mechanism of protein aggregation in ATP-deficient cells and a possible role of transient ischemia in development of tumor thermotolerance in vivo are discussed.
Exp Mol Pathol 1994 Apr
PMID:Induction of heat-shock protein synthesis and thermotolerance in EL-4 ascites tumor cells by transient ATP depletion after ischemic stress. 807 May 44


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