Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high-affinity IgE receptor (Fc epsilon RI), which is expressed on the surface of mast cells and basophils, has a central role in immediate allergic responses. In the rat basophilic leukaemia cell line RBL-2H3, which is a model system for the analysis of Fc epsilon RI-mediated signal transduction, surface engagement of Fc epsilon RI induces histamine release and the tyrosine phosphorylation of several distinct proteins. Although the alpha, beta, and gamma subunits of Fc epsilon RI lack intrinsic tyrosine protein kinase (TPK) activity, a kinase that copurifies with Fc epsilon RI phosphorylates the beta and gamma subunits of the receptor on tyrosine residues. We report here that in RBL-2H3 cells, p56lyn and pp60c-src are activated after Fc epsilon RI crosslinking, and p56lyn coimmunoprecipitates with Fc epsilon RI. In the mouse mast-cell line PT-18, another cell type used to study FC epsilon RI-mediated signalling, tyrosine phosphorylation of proteins is also an immediate consequence of receptor crosslinking. Notably, the only detectable src protein-related TPK in PT-18 cells is p62c-yes, and it is this TPK that is activated on Fc epsilon RI engagement and coimmunoprecipitates with the receptor. Therefore, it seems that different src protein-related TPKs can associate with the same receptor and become activated after receptor engagement.
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PMID:Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. 137 May 75

The gamma subunit of the high affinity IgE receptor, Fc epsilon RI, is a member of a family of proteins which form disulfide-linked dimers. This family also includes the zeta- and eta-chains of the T cell receptor. Engagement of Fc epsilon RI activates src-related protein tyrosine kinases in basophils and mast cells. However, the role of individual subunits of Fc epsilon RI in this activation is still not known. In an effort to determine the function of Fc epsilon RI-gamma, we used chimeric proteins containing the extracellular and transmembrane domains of the alpha chain of the human interleukin 2 receptor (Tac) and the cytoplasmic domains of either T cell receptor-zeta or Fc epsilon RI-gamma. We show that while cross-linking of the Tac chimeras in the rat basophilic leukemia cell line RBL-2H3 resulted in the tyrosine phosphorylation of a subset of proteins and a portion of the degranulation normally observed after Fc epsilon RI-mediated stimulation, no detectable activation of p56lyn or pp60c-src was observed. In contrast, an apparent transient deactivation of these two kinases was observed after Tac chimera cross-linking. These observations suggest that Fc epsilon RI-gamma is responsible for some, but not all, of the signaling that occurs after engagement of its receptor, and that other receptor subunits may also play important roles in this signaling process.
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PMID:Signal transduction by the cytoplasmic domains of Fc epsilon RI-gamma and TCR-zeta in rat basophilic leukemia cells. 138 15

Previous studies have shown that carboxyl-terminal mutation of pp60c-src can activate its transforming ability. Conflicting results have been reported for the transforming ability of pp60c-src mutants having only mutations outside its carboxyl-terminal region. To clarify the effects of such mutations, we tested the activities of chimeric v(amino)- and c(carboxyl)-src (v/c-src) proteins at different dosages in NIH 3T3 cells. The focus-forming activity of Rous sarcoma virus long terminal repeat (LTR)-src expression plasmids was significantly reduced when the v-src 3' coding region was replaced with the corresponding c-src region. This difference was masked when the Rous sarcoma virus LTR was replaced with the Moloney murine leukemia virus LTR, which induced approximately 20-fold more protein expression, but even focus-selected lines expressing v/c-src proteins were unable to form large colonies in soft agarose or tumors in NFS mice. This suggests that pp60c-src is not equally sensitive to mutations in its different domains and that there are at least two distinguishable levels of regulation, the dominant one being associated with its carboxyl terminus. v/c-src chimeric proteins expressed with either LTR had high in vitro specific kinase activity equal to that of pp60v-src but, in contrast, were phosphorylated at both Tyr-527 and Tyr-416. Total cell protein phosphotyrosine was enhanced in cells incompletely transformed by v/c-src proteins to the same extent as in v-src-transformed cells, suggesting that the carboxyl-terminal region may affect substrate specificity in a manner that is important for transformation.
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PMID:v-src mutations outside the carboxyl-coding region are not sufficient to fully activate transformation by pp60c-src in NIH 3T3 cells. 245 Nov 22

We have deduced the sequence of the protein encoded by the chicken c-yes gene from overlapping cDNA clones. The predicted protein, p61c-yes, contains 541 amino acids and has a molecular weight of 60,911 with the amino terminal methionine residue. Chicken p61c-yes differs from Y73 virus p90gag/v-yes in three respects. First, the carboxy-terminal eight amino acids of p61c-yes are replaced by three amino acids in p90gag/v-yes, which are encoded by the avian leukemia virus env gene. This alteration changes the position and context of a tyrosine residue in p61c-yes. Second, nucleotides which are present as 5' non-translated sequence in the p61c-yes mRNA, are translated in the p90gag/v-yes mRNA. Third, there are fourteen dispersed nucleotide differences in Y73 v-yes which result in six amino differences between the body of p90gag/v-yes and p61c-yes. Chicken p61c-yes differs from human p61c-yes at 43 residues, and from chicken pp60c-src at 122 residues.
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PMID:The sequence of chicken c-yes and p61c-yes. 246 85

NIH 3T3 cells were transfected with plasmids containing Moloney murine leukemia virus long terminal repeats and either chicken c-src or v-src genes. In contrast with the effects observed after transfection with plasmids containing c-src and avian retrovirus or simian virus 40 promoter-enhancers (H. Hanafusa, H. Iba, T. Takeya, and F. R. Cross, p. 1-8, in G. F. Vande Woude, A. J. Levine, W. C. Topp, and J. D. Watson, ed., Cancer Cells, vol. 2, 1984; H. Iba, T. Takeya, F. R. Cross, T. Hanafusa, and H. Hanafusa, Proc. Natl. Acad. Sci. U.S.A. 81:4424-4428, 1984; R. C. Parker, R. Swanstrom, H. E. Varmus, and J. M. Bishop, p. 19-26, in G. F. Vande Woude et al., ed., Cancer Cells, vol. 2, 1984; R. C. Parker, H. E. Varmus, and J. M. Bishop, Cell 37:131-139, 1984; D. Shalloway, P. M. Coussens, and P. Yaciuk, p. 9-17, in G. F. Vande Woude et al., ed., Cancer Cells, vol. 2, 1984; D. Shalloway, P. M. Coussens, and P. Yaciuk, Proc. Natl. Acad. Sci. U.S.A. 81:7071-7075; and K. C. Wilhelmsen, W. G. Tarpley, and H. M. Temin, p. 303-308, in G. F. Vande Woude et al., ed., Cancer Cells, vol. 2, 1984), we found that both types of Moloney murine leukemia virus long terminal repeat-src expression plasmids induced focus formation, although c-src induced only 1% as many foci as v-src. The focus-selected c-src overexpressed cells had altered morphology and limited growth in soft agarose but were not tumorigenic in vivo. Cleveland digests, comparative in vitro kinase assays, secondary transfections, and immunoprecipitations indicated that focus formation was caused by rare transfection events that resulted in very high-level pp60c-src expression rather than by mutations of the transfected c-src genes. These results suggest that pp60v-src induced transformation is not a completely spurious activity which is unrelated to the function of pp60c-src but that it represents a perturbation of already existent molecular control processes involving pp60c-src.
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PMID:Overexpressed pp60c-src can induce focus formation without complete transformation of NIH 3T3 cells. 258 37

The proto-oncogene c-src, the cellular homolog of the Rous sarcoma virus (RSV) transforming gene v-src, is expressed in a tissue-specific and age-dependent manner. Its physiological function, although still unknown, appears to be more closely related to differentiation processes than to proliferation processes. To obtain more information about the physiological role of the c-src gene in cells, we have studied differentiation-dependent alterations using the human HL-60 leukaemia cell line as a model system. Induction of monocytic and granulocytic differentiation of HL-60 cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) and dimethylsulfoxide (DMSO) is associated with an activation of the pp60c-src tyrosine kinase, but not with increased c-src gene expression. Control experiments exclude an interaction of TPA and DMSO themselves with the pp60c-src kinase.
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PMID:Activation of the pp60c-src kinase during differentiation of monomyelocytic cells in vitro. 301 21

We have recently cloned a cDNA from the human T-cell leukemia, JURKAT, having homology with the src-like family of protein-tyrosine kinases. We have made rabbit polyclonal antibodies against the synthetic peptide CKERPEDRPTFDYLRSVLEDFFTATEGQYQPQP (cys-33-pro) deduced from the carboxy-terminal amino acid sequence predicted by the JURKAT cDNA. In this report, we demonstrate that these antibodies immunoprecipitate the protein-tyrosine kinase activity from solubilized membrane extracts from JURKAT T-leukemia cells and from human peripheral blood T-lymphocytes from normal donors. A 58 kd protein, exhibiting protein-tyrosine kinase activity, was specifically immunoprecipitated in both cases. The antibodies failed to crossreact with pp60c-src from human platelets, but did crossreact with the murine T-lymphocyte protein-tyrosine kinase, pp56T-cell.
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PMID:Identification of the human T-lymphocyte protein-tyrosine kinase by peptide-specific antibodies. 349 Aug 47

To elucidate the role of pp60c-src in U937 human monoblastoid leukemia cell proliferation, recombinant plasmids containing the src gene or myb gene, which could produce antisense src or antisense myb RNA after dexamethasone treatment, were constructed and transfected into U937 cells (U937-ASRC, U937-AMYB). pp60c-src synthesis in U937-ASRC was diminished by the third day after induction of antisense src RNA and the cell proliferation was reduced, furthermore, the amount of p75c-myb was significantly decreased by the third day. p75c-myb synthesis in U937-AMYB was diminished by the second day after induction of antisense myb RNA and the cell growth was significantly inhibited but the amount of pp60c-src in U937-AMYB was not reduced. These results suggest that a decrease in the amount of pp60c-src leads to an inhibition of p75c-myb expression and subsequent reduction in the U937 cell proliferation.
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PMID:Antisense src expression inhibits U937 human leukemia cell proliferation in conjunction with reduction of c-myb expression. 751 55

We constructed a recombinant plasmid which expresses antisense src RNA in human cells and used it as a tool for investigating the role of pp60c-src in proliferation and differentiation of K562 human leukemia cells. In erythropoietin (EPO)-responsive cells, EPO induces rapid tyrosine phosphorylation of several cellular proteins including EPO receptor (EPOR) although EPOR has no tyrosine kinase domain. Here we show that antisense src RNA expression suppresses pp60c-src synthesis in the recombinant plasmid-transfected K562 cells, reduces the proliferation and inhibits hemoglobin synthesis and glycophorin A expression promoted by EPO in K562 cells. These findings suggest that pp60c-src plays crucial roles in the proliferation and EPO-induced erythroid differentiation of K562 cells.
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PMID:Antisense src expression inhibits proliferation and erythropoietin-induced erythroid differentiation of K562 human leukemia cells. 751 73

We investigated the effect of ubenimex on the growth and differentiation of U937 cells, a histiocytic lymphoma cell line. Ubenimex is a dipeptide ((2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine) and an inhibitor of aminopeptidase B produced by Streptomyces olivoreticuli. Ubenimex inhibited the proliferation of U937 cells in a dose-dependent manner. Ubenimex-treated U937 cells showed condensation of nuclear chromatin, increase of cytoplasmic vacuoles and more intense nonspecific esterase staining compared with untreated U937 cells. Expression of CD13 and CD68 detected by monoclonal antibodies My7 and EBM11, respectively, was enhanced by ubenimex, but the expression of CD4 detected by MT310 was significantly decreased. The effects of ubenimex on U937 cell growth inhibition and enhancement of monocytic cell surface marker expression on U937 cells were reversible when cultivated without ubenimex for more than 6 days. In addition, the bactericidal activity of U937 cells was increased by ubenimex treatment, and was further enhanced by treatment with macrophage colony-stimulating factor (M-CSF). Furthermore, ubenimex augmented the expression of M-CSF receptors by U937 cells and enhanced the tyrosine kinase activity of cellular pp60c-src. These findings indicated that ubenimex inhibited the proliferation of U937 cells and induced morphological, cytochemical and functional differentiation into monocyte/macrophages.
Leukemia 1994 Dec
PMID:Effect of ubenimex on the proliferation and differentiation of U937 human histiocytic lymphoma cells. 752 60


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