Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An underinvestigated aspect of the mitogenic and cell regulatory actions of vanadium is the regulation of gene expression. Among the fifteen cellular genes studied in cultured mouse C127 cells, vanadium (as 10 microM sodium vanadate) increased levels of mRNA of the actin and c-Ha-ras to four times control values. These increases represented de novo synthesis of mRNA, since they were inhibited by actinomycin D. Vanadate did not increase mRNA corresponding to c-src, c-mos, c-myc, p53, HSP70, pODC or RB genes, and expression of c-erb A, c-erb B, c-sis and c-fes genes was undetectable whether vanadium was present or not. Expression of a third gene affected by vanadium, c-jun, was augmented by addition of a reductant or oxidant together with the vanadate. Addition of NADH (marginally effective on its own) or H2O2 (effective alone) dramatically enhanced the effect of vanadate on c-jun gene expression. Catalase inhibited the effect of NADH partly. The vanadate-stimulated expression of actin and c-Ha-ras mRNA were unaffected by oxidants, reductants, metal chelators, or anti-oxidant enzymes. Evidently vanadate acts by two separate mechanisms on these two categories of genes. The alternate hypothesis that the actions of vanadate on actin and c-Ha-ras were mediated by a protein kinase cascade was inconsistent with the following observations. Neither insulin nor epidermal growth factor increased mRNA levels of c-Ha-ras or actin gene. Neither genistein (a tyrosine kinase inhibitor) nor pretreatment with 12-O-tetradecanoylphorbol-13-acetate blocked the actions of vanadate on these genes. Clearly the biological actions of vanadium depend in part on altered expression of genes. Since two of the genes are proto-oncogenes, this mechanism is potentially relevant to the mitogenic responses of cells to vanadium.
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PMID:Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species. 143 69

Myeloblast cell line K562, when stably transfected with the human genomic c-fes sequence encoding a proto-oncogene tyrosine-protein kinase, acquires the characteristics of more mature granulocytic cells (WS-1 cells) and the ability to undergo differentiation (Yu, G., Smithgall, T. E., and Glazer, R. I. (1989) J. Biol. Chem. 264, 10276-10281). To explore the role of transcription factors in the differentiation process, WS-1 cells were analyzed for the presence of DNA-binding proteins capable of interacting with the 5'-long terminal repeat (LTR) region of human immunodeficiency virus (HIV)-1, that contains the binding sequences for transcription factors Sp1 and NFKB. Southwestern blotting and mobility shift assays revealed the presence of Sp1 in K562 and WS-1 cells. The DNA-binding activity of Sp1 was significantly greater in WS-1 cells than in K562 cells, despite the detection by immuno-blotting of equivalent quantities and degrees of heterogeneity of Sp1 in both cell lines. DNA footprinting of the HIV-1 5'-LTR demonstrated that two of the three Sp1-binding sites and both NFKB binding sequences were protected by nuclear extracts from WS-1 cells, while no protection was afforded by nuclear extracts from K562 cells. Analysis of transcription in vitro by primer extension revealed enhanced initiation of transcription from the HIV-1 5'-LTR by nuclear extracts from WS-1 cells, but not from K562 cells. These data indicate that the response evoked by the c-fes tyrosine-protein kinase leads to enhanced DNA binding activity of Sp1 and NFKB, that results in the activation of transcription from the HIV-1 5'-LTR.
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PMID:Increased DNA binding and transcriptional activity associated with transcription factor Sp1 in K562 cells transfected with the myeloid-specific c-fes tyrosine kinase gene. 187 37

The avian c-fps and mammalian c-fes proto-oncogenes are cognate cellular sequences. Antiserum raised against the P140gag-fps transforming protein of Fujinami avian sarcoma virus specifically recognized a 92,000-Mr protein in human and mouse hematopoietic cells which was closely related in structure to Snyder-Theilen feline sarcoma virus P87gag-fes. This polypeptide was apparently the product of the human c-fes gene and was therefore designated p92c-fes. Human p92c-fes was associated with a tyrosine-specific protein kinase activity in vitro and was capable of both autophosphorylation and phosphorylation of enolase as an exogenous protein substrate. The synthesis of human and mouse p92c-fes was largely, though not entirely, confined to myeloid cells. p92c-fes was expressed to relatively high levels in a multipotential murine myeloid cell line, in more mature human and mouse granulocyte-macrophage progenitors, and in differentiated macrophage like cells as well as in the mononuclear fraction of normal and leukemic human peripheral blood. p92c-fes was not found in erythroid cells, with the exception of a human erythroleukemia line which retains the capacity to differentiate into macrophage like cells. These results suggest a normal role for the p92c-fes tyrosine kinase in hematopoiesis, particularly in granulocyte-macrophage differentiation. In addition, a distinct 94,000-Mr polypeptide, antigenically related to p92c-fes, was identified in a number of hematopoietic and nonhematopoietic human and mouse cells and was also found to be associated with a tyrosine-specific protein kinase activity.
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PMID:Expression of the mammalian c-fes protein in hematopoietic cells and identification of a distinct fes-related protein. 242 71

The protein kinase domains of v-kit, the oncogene of the acute transforming feline retrovirus HZ4-FeSV (HZ4-feline sarcoma virus), CSF-1R (macrophage colony stimulating factor receptor) and PDGFR (platelet derived growth factor receptor) display extensive homology. Because of the close structural relationship of v-kit, CSF-1R and PDGFR we predicted that c-kit would encode a protein kinase transmembrane receptor (Besmer et al., 1986a; Yarden et al., 1986). We have now determined the primary structure of murine c-kit from a DNA clone isolated from a brain cDNA library. The nucleotide sequence of the c-kit cDNA predicts a 975 amino acid protein product with a calculated mol. wt of 109.001 kd. It contains an N-terminal signal peptide, a transmembrane domain (residues 519-543) and in the C-terminal half the v-kit homologous sequences (residues 558-925). c-kit therefore contains the features which are characteristic of a transmembrane receptor kinase. Comparison of c-kit, CSF-1R and PDGFR revealed a unique structural relationship of these receptor kinases suggesting a common evolutionary origin. The outer cellular domain of c-kit was shown to be related to the immunoglobulin superfamily. The sites of expression of c-kit in normal tissue predict a function in the brain and in hematopoietic cells. N-terminal sequences which include the extracellular domain and the transmembrane domain as well as 50 amino acids from the C-terminus of c-kit are deleted in v-kit. These structural alterations are likely determinants of the oncogenic activation of v-kit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family--oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. 245 20

The protein encoded by v-fms, the oncogene of the Susan McDonough strain of feline sarcoma virus, is a member of the protein tyrosine kinase family. The kinase activity of the v-fms encoded protein has been reported to be low compared to other members of this enzyme family. We found that the optimal pH in vitro for the autophosphorylation of the immunoprecipitated v-fms encoded protein kinase activity was about pH 5.0; the activity at this pH was 15-fold higher than at the pH (7.4) used in standard kinase assays. The low pH optimum of the kinase activity of the v-fms encoded protein was observed when this protein was immunoprecipitated with each of four independent polyclonal antisera. v-fms proteins from transfected rat, mink or hamster cells all showed the same pH optimum for the kinase activity, as did the protein encoded by the feline c-fms gene. Autophosphorylation of v-fms in vitro at pH 5.0 occurred exclusively on tyrosine residues. Enolase was a substrate for the v-fms encoded protein kinase, and the pH profile for phosphorylation of this substrate in vitro paralleled that seen for the autophosphorylation of v-fms encoded proteins. The discovery of the low pH optimum of the kinase activity exhibited by v-fms proteins may be useful for further characterization of this activity in vitro, as well as for phenotypic classification of other members of the protein tyrosine kinase family.
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PMID:The kinase activity of the v-fms encoded protein has a low pH optimum. 265 15

The macrophage colony-stimulating factor, CSF-1 (M-CSF), is a homodimeric glycoprotein required for the lineage-specific growth of cells of the mononuclear phagocyte series. Apart from its role in stimulating the proliferation of bone marrow-derived precursors of monocytes and macrophages, CSF-1 acts as a survival factor and primes mature macrophages to carry out differentiated functions. Each of the actions of CSF-1 are mediated through its binding to a single class of high-affinity receptors expressed on monocytes, macrophages, and their committed progenitors. The CSF-1 receptor (CSF-1R) is encoded by the c-fms proto-oncogene, and is one of a family of growth factor receptors that exhibits an intrinsic tyrosine-specific protein kinase activity. Transduction of c-fms sequences as a viral oncogene (v-fms) in the McDonough (SM) and HZ-5 strains of feline sarcoma virus has resulted in alterations in receptor coding sequences that affect its activity as a tyrosine kinase and provide persistent signals for cell growth in the absence of its ligand. The genetic alterations in the c-fms gene that unmask its latent transforming potential abrogate its lineage-specific activity and enable v-fms to transform a variety of cells that do not normally express CSF-1 receptors.
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PMID:Colony-stimulating factor-1 receptor (c-fms). 285 67

The HZ2-feline sarcoma virus (HZ2-FeSV) is a replication-defective acute transforming feline retrovirus with oncogene homology to Abelson murine leukemia virus (A-MuLV) (P. Besmer, W.D. Hardy,Jr., E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Jr. (1983) Nature (London) 303, 825-828). In contrast to A-MuLV which was isolated from a hematopoietic tumor, the HZ2-FeSV derives from a multicentric fibrosarcoma. We have molecularly cloned the HZ2-FeSV provirus from mink HZ2-FeSV nonproducer cells. The molecularly cloned HZ2-FeSV provirus is biologically active upon transfection of NIH 3T3 indicator cells. The genetic structure of the HZ2-FeSV provirus was determined by EM heteroduplex and Southern blot analysis. The HZ2-FeSV has a 6.8 kb-viral genome with the structure: 5' delta gag-abl-delta pol-delta env 3'. The abl insert, which is 1.4 kb, is located 1.9 kb from the 5' end and 3.5 kb from the 3' end of the viral genome. The 5' 1.9 kb in the HZ2-FeSV are colinear with 5' FeLV sequences, and the 3' 3.5 kb are colinear with 3' FeLV sequences, with the exception of a 0.85-kb deletion in the env gene. HZ2-FeSV v-abl and A-MuLV v-abl share 1.2 kb of abl sequences which are known to specify the protein kinase domain of the abl gene product and are necessary for fibroblast transformation in vitro. The DNA from several tumor tissues of cat 3590 from which the HZ2-FeSV was obtained was found to contain several HZ2-FeSV-related proviruses including the HZ2-FeSV. The variant HZ2-FeSVs have indistinguishable 5' gag-abl sequences; however, they differ in 3' sequences which likely do not include any abl sequences. The DNAs from fibrosarcomas obtained by inoculation of kittens with tumor extract were found to contain variant HZ2-FeSV proviruses as well. Taken together these results indicate a role for the HZ2-FeSVs in sarcomagenesis.
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PMID:Structure and origins of the HZ2-feline sarcoma virus. 288 77

The feline c-fes proto-oncogene, different parts of which were captured in feline leukemia virus (FeLV) to generate the transforming genes (v-fes) of the Gardner-Arnstein (GA) strain of feline sarcoma virus (FeSV) and the Snyder-Theilen strain (ST) of FeSV, was cloned and its genetic organization determined. Southern blot analysis revealed that the c-fes genetic sequences were distributed discontinuously and colinearly with the v-fes transforming gene over a DNA region of around 12.0 kb. Using cloned c-fes sequences, complementation of GA-FeSV transforming activity was studied. Upon replacement of the 3' half of v-fesGA with homologous feline c-fes sequences and transfection of the chimeric gene, morphological transformation was observed. Immunoprecipitation analysis of these transformed cells revealed expression of high Mr fusion proteins. Phosphorylation of these proteins was observed in an in vitro protein kinase assay, and tyrosine residues appeared to be involved as acceptor amino acid.
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PMID:Molecular cloning of the feline c-fes proto-oncogene and construction of a chimeric transforming gene. 299 4

The cell-derived domain of Gardner-Rasheed feline sarcoma virus (GR-FeSV) consists of a gamma-actin- and a tyrosine-specific protein kinase-encoding sequence designated v-fgr. By utilizing a v-fgr probe, it was possible to detect related sequences present at low copy number in DNAs of a variety of mammalian species and to isolate a human fgr homologue. Comparative studies revealed that this human DNA clone represented all but 200 base pairs of v-fgr. Analysis of human genomic DNA demonstrated that the fgr protooncogene was distinct from the cellular homologues of other retrovirus onc genes. In addition, the fgr protooncogene was localized to the distal portion of the short arm of human chromosome 1 at p36.1-36.2 by in situ hybridization. Taken together, our findings establish that the fgr protooncogene is a unique member of the tyrosine kinase gene family.
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PMID:Isolation and chromosomal localization of the human fgr protooncogene, a distinct member of the tyrosine kinase gene family. 299 72

A new acute transforming feline retrovirus, the Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), has been isolated from a feline fibrosarcoma. The viral genome of HZ4-FeSV contains a new oncogene designated v-kit, has the structure 5' delta gag-kit-delta pol-delta env 3' and specifies a gag-kit polyprotein of relative molecular mass 80,000. The predicted kit amino-acid sequence displays partial homology with tyrosine-specific protein kinase oncogenes. HZ4-FeSV appears to have been generated by transduction of feline c-kit sequences with feline leukaemia virus.
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PMID:A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. 300 97


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