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 endocytosis of the T cell differentiation antigen CD4 has been investigated in CD4-transfected HeLa cells, the promyelocytic HL-60 cell line, and in a number of leukemia- or lymphoma-derived T cell lines. CD4 internalization was followed using radioiodinated antibodies in an acid-elution endocytosis assay, or by covalently modifying cell surface proteins with biotin and analyzing CD4 distributions by immunoprecipitation; both approaches gave equivalent results. The assays demonstrated that in transfected HeLa cells and in HL-60 cells CD4 was constitutively internalized and recycled in the absence of ligand. Immunogold labeling and electron microscopy demonstrated that CD4 enters cells through coated pits. In contrast to the nonlymphocytic cells, T cell lines showed very little endocytosis of CD4. Measurements of fluid phase endocytosis and morphometric analysis of the endosome compartment indicated that the endocytic capacities of HeLa and lymphoid cells are equivalent and suggested that the low level of CD4 uptake in lymphocytic cells is due to exclusion of CD4 from coated pits. This conclusion was supported by experiments using truncated CD4 molecules, lacking the bulk of the cytoplasmic domain, which were internalized equally efficiently in both transfected lymphocytes and HeLa cells. Together, these results indicate that the cytoplasmic domain of CD4 mediates the different interactions with the endocytic apparatus in lymphoid and nonlymphoid cells. We suggest that the CD4-associated lymphocyte-specific protein tyrosine kinase p56lck may be involved in preventing CD4 endocytosis in T cells.
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PMID:Differential endocytosis of CD4 in lymphocytic and nonlymphocytic cells. 190 77

The T-lymphocyte-specific tyrosine kinase gene, lck, is expressed in T-lymphocyte cell lines, except for several human T-cell leukemia virus type I(HTLV-I)-transformed T-lymphocyte cell lines, which produce HTLV-I. By introducing an lck-expression vector, we found that lck product suppresses gene expression from HTLV-I promoter in a transient assay. Moreover, various other promoters of cellular genes or viruses were found to have their transcriptional activity repressed by lck.
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PMID:lck suppresses gene expression from various promoters including human T-cell leukemia virus type I promoter. 211 90

We have previously reported that lck mRNA (a lymphocyte-specific protein tyrosine kinase gene) is absent in human T-cell leukemia virus type I (HTLV-I)-infected interleukin-2(IL-2)-independent T-cell lines, while HTLV-I-negative T-cell lines and HTLV-I-positive IL-2-dependent ones express a large amount of lck mRNA. To further investigate the levels of lck expression, we prepared rabbit anti-Lck antiserum directed against the synthetic oligopeptide of 32 amino acids corresponding to the carboxy terminus of this gene product, p56lck. Using this antiserum, we show that HTLV-I-positive T-cell lines, whether they are IL-2-dependent or not, scarcely express p56lck. In other words, IL-2-dependent HTLV-I-positive T-cell lines seldom produce p56lck in spite of high expression of lck mRNA. Absence of p56lck is suspected of playing an important role in malignant transformation of HTLV-I-infected T-cells.
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PMID:Human T-cell leukemia virus type-I-infected T-cell lines scarcely produce p56lck, whether or not they express lck mRNA. 238 77

The human T-cell- or lymphocyte-specific gene, lck, encodes a tyrosine kinase and is a member of the src family. In this report we demonstrate that there are two classes of human lck transcripts (types I and II), containing different 5'-untranslated regions, which are expressed from two distinct promoters. No apparent sequence similarity was observed between the 5'-flanking regions of the two promoters. The expression of lck in human T-cell leukemia and carcinoma cell lines and in human peripheral blood T lymphocytes was examined by S1 nuclease and primer extension mapping and by Northern (RNA) blot analysis of total cellular RNA. The following results were obtained. (i) Two RNA start sites in the downstream promoter were used to generate type I transcripts. (ii) The major human type I start site has not been described for the mouse. (iii) At least five RNA start sites in the upstream promoter were used to generate type II transcripts. (iv) In T cells and in two colon carcinoma cell lines, type II transcripts were present in higher amounts than type I transcripts. (v) In T cells treated with phytohemagglutinin, tetradecanoylphorbol acetate, and cyclosporin A, the modulation of lck expression was associated primarily with changes in levels of type II transcripts. The above results suggest that the two human lck promoters are utilized differentially and may be regulated independently during certain physiological states.
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PMID:Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells. 278 74

p56lck, a member of the src family of cytoplasmic tyrosine protein kinases, is expressed primarily in lymphoid cells. Previous RNase protection data demonstrated the existence of at least two lck mRNAs (type I and type II) with different 5' untranslated regions in most T cells. These have been found here to arise from two separate promoters. S1 nuclease analysis and primer extension were used to locate the site of initiation of type I lck mRNA. The nucleotide sequence of the region upstream of this start site contains no classical promoter motifs. A cDNA clone of type II lck mRNA was isolated. The promoter of this mRNA must be more than 10 kilobases upstream of the type I promoter region. In two murine thymoma cell lines, LSTRA and Thy19, lck is expressed at elevated levels as a result of Moloney murine leukemia virus retrovirus promoter insertion. p56lck is encoded in these cells by a hybrid virus-lck mRNA containing the 5' untranslated region of Moloney virus mRNA. The structures and the sites of integration of the proviruses upstream of lck in these cells were examined by molecular cloning and Southern analysis. A truncated and rearranged provirus, flanked by 554 nucleotides (nt) of duplicated cellular sequences, was found 962 nt upstream of the start site for type I lck mRNA in LSTRA cells. What appears to be a Moloney mink cytopathic focus-forming provirus was found between 584 to 794 nt upstream of the start site for type I lck mRNA in Thy19 cells. Thus in both tumor cell lines, viral DNA is present between the promoters for type I and type II lck mRNAs. Comparison of the sequences of the 5' ends of the lck and c-src genes suggests that divergence of these two genes involved exon shuffling and that a homolog of the neuronal c-src(+) exon is not present in lck.
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PMID:Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promoters. 284 26

The lck gene encodes a lymphocyte-specific protein-tyrosine kinase that is implicated in neoplastic transformation. We have determined the germ line organization of the murine lck gene and have isolated and characterized a rearranged lck allele in the murine lymphoma cell line LSTRA. The overall exon-intron organization of the normal lck gene is almost identical to that of avian c-src. In LSTRA DNA, an internally rearranged Moloney murine leukemia virus genome is interposed between two distinct promoters that normally generate lck transcripts differing only in 5' untranslated regions. The rearrangement appears to have been selected to permit splicing of transcripts that initiate from the Moloney virus promoter to an acceptor site located within the first exon 3' to the downstream promoter, thus generating an lck mRNA with a novel 5' untranslated region that may be more efficiently translated.
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PMID:Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. 285 Apr 79

Dsi-1 is a region of chromosomal DNA that underwent proviral insertion in 3 of 24 Moloney murine leukemia virus-induced rat thymomas. In one of these tumors, a provirus is also integrated adjacent to the proto-oncogene c-myc. The proviruses in Dsi-1 have been characterized and appear to be complete. The proviruses were located within a 2-kilobase region that contained four prominent DNase I-hypersensitive sites. These hypersensitive sites were observed in Moloney murine leukemia virus-induced thymomas but not in NRK cells. The region of Dsi-1 immediately 3' to the insertions cross-hybridized with human and chicken DNA, indicating that it contains highly conserved sequences. No evidence could be found for the expression of this highly conserved region. Dsi-1 was mapped to mouse chromosome 4. This location demonstrates that Dsi-1 is different from 16 of the known proto-oncogenes (c-abl, c-erbA c-erbB, c-ets-1, c-ets-2, c-fes, c-fos, c-myb, c-myc, c-raf, A-raf, c-Ha-ras, c-Ki-ras, N-ras, c-sis, and c-src) and 12 cellular regions of tumor-associated integrations in retrovirus-induced tumors (c-erbB, Fis-1, int-1, int-2, Mis-1/pvt-1, Mlvi-1, Mlvi-2, c-mos, c-myb, c-myc, Pim-1, and c-Ha-ras). Hybridization experiments indicated that Dsi-1 is probably different from five additional proto-oncogenes (c-fgr, c-fms, c-mos, neu, and c-yes) and from two additional frequent integration regions (lck and Mlvi-3).
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PMID:Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. 302 11

To evaluate the role of the human T-cell-specific tyrosine kinase lck (YT16), we measured the levels of lck expression in thymocytes, peripheral T-cells, and leukemia T-cell lines which are arrested at different stages of thymic differentiation. The results indicate that higher levels of the lck message can be found in total thymocytes and T-cells arrested at Stage III (thymocytes that have rearranged their alpha, beta, and gamma chain T-cell receptor genes). A 20-fold lower level of these transcripts, however, can be found in cells derived from Stage I cells (thymocytes with germline alpha, beta, and gamma genes), 4 times less messages in Stage II cells (thymocytes with rearranged gamma and beta chain genes, but with germline alpha chain genes), and a 4-fold lower amount of RNA in Stage IV cells (mature lymphocytes). Culture of these cells with a variety of inducing reagents indicated that leukemia cell lines of only Stages I and II can be induced to increase their levels of YT16 expression by the addition of tetradecanoyl phorbol-13-acetate. These results suggest that there may be a developmental regulation of these tyrosine kinase messages during T-cell ontogeny. The high level of these transcripts in more mature T-cell leukemia lines suggests that they may primarily play a role in the proliferative controls of these cells.
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PMID:Expression of the human T-cell-specific tyrosine kinase YT16 (lck) message in leukemic T-cell lines. 325 10

We report the isolation and nucleotide sequence of a 3.7-kilobase (kb) cDNA clone from chicken spleen corresponding to a previously undescribed member of the src family of protooncogenes. It encodes a protein with a C-terminal domain related to the src family of protein-tyrosine kinases (EC 2.7.1.112) and, among these, has most significant homology to the lck gene isolated from a murine leukemia virus-induced thymoma cell line. The gene is therefore referred to as c-tkl for cellular tyrosine kinase related to lck. Analysis of genomic DNA reveals that c-tkl is a chromosomal locus distinct from c-src and c-lck. Furthermore, the size of c-tkl mRNA as well as its pattern of expression indicates that it is not the chicken homologue of lck but a different gene. A 3.8-kb transcript of the c-tkl gene, identical to the size determined for c-src mRNA, was observed in cultured chicken embryo fibroblasts and in chicken spleen and brain. In contrast, detection of a definite c-src mRNA signal with mRNA from spleen was not possible under the hybridization conditions employed when the 5' end of v-src was used as the probe, and none of the 11 clones obtained from the cDNA library corresponded to a c-src transcript. Thus previous studies of c-src mRNA expression in spleen may have actually detected c-tkl transcripts.
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PMID:Additional member of the protein-tyrosine kinase family: the src- and lck-related protooncogene c-tkl. 332 Oct 53

The murine lck gene is closely related to a family of cellular protooncogenes and encodes a lymphocyte-specific, membrane-associated protein tyrosine kinase. We and others have demonstrated that the lck gene is rearranged and overexpressed in the murine lymphoma LSTRA, most likely as a result of the insertion of Moloney murine leukemia virus DNA immediately adjacent to the gene. We now report that the lck gene is located at the distal end of murine chromosome 4 and on human chromosome 1 at position 1p32-35 near a site of frequent structural abnormalities in human lymphomas and neuroblastomas. These results raise the possibility that structural alteration of the lck gene through chromosomal rearrangement may contribute to transformation in human malignant disease.
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PMID:Localization of a lymphocyte-specific protein tyrosine kinase gene (lck) at a site of frequent chromosomal abnormalities in human lymphomas. 346 75


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