Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NRK cells transformed by the McDonough strain of feline sarcoma virus (SM-FeSV) were mutagenized by the use of 5'-azacytidine. Four cell lines expressing different transformation-defective phenotypes were isolated. Superinfection of these cell lines with simian sarcoma-associated virus (SSAV) led in three instances to the recovery of transforming virus particles carrying an intact fms gene. A nonconditional transformation-defective virus, designated td26-SM-FeSV (SSAV), was isolated from one of the cell lines. NRK cells infected with this mutant contained actin cables and fibronectin networks and exhibited normal cell morphology. Such cells formed only small colonies in soft agar and exhibited a mitogenic activity similar to that of noninfected cells. Cells infected with td26-SM-FeSV (SSAV) synthesized a gag-fms fusion glycoprotein (gp180gag-fms). This polypeptide was processed in the normal manner into the intracellular gp120v-fms and a transformation-defective gp140td-v-fms which was expressed at the surface of infected cells. This species had an increased electrophoretic mobility on polyacrylamide gels compared with the molecule from wild-type virus.gp140td-v-fms had endo-beta-N-acetylglucosaminidase H-resistant carbohydrate side chains. No tyrosine kinase activity was detectable in vivo in td26-SM-FeSV (SSAV)-infected cells even when the cells were treated with sodium orthovanadate. In vitro, fms molecules from td26-SM-FeSV (SSAV)-infected cells exhibited tyrosine kinase activity as determined by autophosphorylation and phosphorylation of exogenous (poly)Glu-Tyr. At low ATP concentrations (less than 5 microM) this in vitro tyrosine kinase activity was significantly reduced compared with that of the wild-type counterpart.
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PMID:Isolation of a transformation-defective mutant of the McDonough strain of feline sarcoma virus exhibiting tyrosine kinase activity in vitro but not in vivo. 283 15

Murine epidermal growth factor (EGF) is synthesized as part of a large precursor (pro-EGF), which is thought to span the cell membrane. Comparison of the published pro-EGF sequence with the sequences of the translation products of viral oncogenes reveals that pro-EGF is related to the translation product of mos, the oncogene of Moloney murine sarcoma virus. Similarity is greatest between the COOH-terminal region of v-mos (residues 317-360) and part of the cytoplasmic domain of pro-EGF (residues 1127-1174). Statistical comparison of these sequences indicates that the probability of the similarity arising by chance is less than 2 X 10(-8). This similarity extends to the corresponding regions of the translation products of the cellular homologues (c-mos) of the v-mos gene present in normal murine and human DNA. Similarities are also observed between two other regions of the murine c-mos sequence (residues 48-134 and 196-275) and parts of the extracellular domain of pro-EGF (residues 565-651 and 741-817, respectively). All three mos genes are members of the tyrosine kinase family of oncogenes, as is erbB, the oncogene of avian erythroblastosis virus. Since the sequences of the erbB translation product and the EGF receptor are closely related, the relationship between mos and pro-EGF suggests that pro-EGF and the EGF receptor have evolved from a common ancestor.
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PMID:Epidermal growth factor precursor is related to the translation product of the Moloney sarcoma virus oncogene mos. 298 73

We have found that both an antibody directed against a synthetic peptide representing an amino acid sequence of the conserved kinase domain of transforming protein P140 of Fujinami sarcoma virus and a regressing tumor antiserum recognized the products of the c-fps/fes genes of both avian and mammalian cells. The anti-peptide antibody also recognized a 94-kilodalton protein that was related to but distinct from the c-fps/fes product in structure and in tissue distribution. A 92-kilodalton protein, NCP92, was found to be the mammalian counterpart of the previously identified avian c-fps/fes protein NCP98 by its structural similarity to NCP98, its associated tyrosine kinase activity, and its similar tissue distribution. The highest levels of NCP92 were found in tissue macrophages and in bone marrow. In bone marrow NCP92 expression was restricted to cells of the monocyte/macrophage and granulocyte lineages. That the expression of NCP92 is limited to these cell types was confirmed by the analysis of murine and human hematopoietic tumors representing different cell lineages: NCP92 was positive in leukemic cells of granulocytic and monocytic origin but not in B-lymphocytic, T-lymphocytic, or erythroid tumor cells. The expression of NCP92 seems to be related to the capacity of myeloid cells to differentiate and to respond to certain colony-stimulating factors.
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PMID:Specific expression of the human cellular fps/fes-encoded protein NCP92 in normal and leukemic myeloid cells. 298 15

Recent studies of platelet-derived growth factor (PDGF) have revealed several structural and functional similarities between this growth factor or components linked to its mechanism of action and certain oncogene products: PDGF itself has a structural homology with the transforming protein of simian sarcoma virus, the PDGF receptor has a functional homology (tyrosine kinase activity) with a family of oncogene products, and PDGF induces the expression of the cellular counterparts of myc and fos. In addition, several tumour cell lines have been found to produce PDGF-like growth factors, which may cause autocrine stimulation of growth. We interpret these findings as indicating that regulatory components along the PDGF-dependent mitogenic pathway may have oncogenic properties if they are inappropriately expressed or activated.
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PMID:Platelet-derived growth factor: mechanism of action and relation to oncogenes. 301 26

A library of chicken genomic DNA was screened for sequences that could hybridize to a cloned DNA fragment containing the transforming gene (v-fps) of Fujinami sarcoma virus. In addition to c-fps, two unique chicken cellular DNA sequences were isolated that hybridized weakly to v-fps. These sequences hybridized with many other viral oncogenes encoding tyrosine kinases. Sequence analysis of the region where homology was detected revealed a region that is highly conserved among the tyrosine kinases both at the nucleotide and amino acid levels. Although we were unable to detect expression of either chicken cellular DNA sequence in a variety of avian tissues, the data suggest the existence of additional members of the tyrosine kinase gene family. Screening genomic libraries for sequences that hybridize weakly to functional regions of other genes may prove useful for the isolation and characterization of additional members of other gene families.
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PMID:Isolation of chicken cellular DNA sequences with homology to the region of viral oncogenes that encodes the tyrosine kinase domain. 302 34

We raised antibodies directed against a synthetic peptide representing an amino acid sequence of the conserved kinase domain of the transforming protein of Fujinami sarcoma virus (FSV) (P140). The antiserum obtained specifically recognized FSV-P140 and its cellular homolog and in addition, it recognized a new cellular protein of 94,000 daltons (NCP94) in avian and mammalian cells. NCP94 was found to be associated with a cyclic nucleotide-independent protein kinase activity that was specific for tyrosine residues. Although NCP94 and FSV-P140 share antigenic determinants, NCP94 is not a cellular homolog of FSV-P140: NCP94 and the previously identified c-fps/fes product were different in their tryptic fingerprints and in their tissue specificities. Thus, the function of NCP94 in normal cells is probably different than that of the c-fps/fes product. NCP94 was expressed in every tissue and cell line that was examined. In chickens, NCP94 levels were highest during embryonic development and NCP94 expression was high in gizzard, brain, and spleen throughout embryonic and adult life. The universal expression of NCP94 suggests that this protein may be involved in an essential function of normal cells. NCP94 may be a new cellular tyrosine kinase of the src gene family.
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PMID:Antipeptide antiserum identifies a widely distributed cellular tyrosine kinase related to but distinct from the c-fps/fes-encoded protein. 302 66

We isolated a human gene (designated c-ros-1) homologous to the v-ros sequence of UR2 sarcoma virus. Ten exons, 1,414 base pairs spanning 26 kilobases, contained a tyrosine kinase domain, a transmembrane domain, and a part of an extracellular domain carrying an N glycosylation site which was not acquired by UR2 sarcoma virus. The predicted structure of c-ros-1 is unique among the src family and clearly distinct from the human insulin receptor.
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PMID:Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule. 302 56

Site-directed mutagenesis of the Fujinami sarcoma virus (FSV) genome has suggested that Tyr 1073 of the P130gag--fps protein-tyrosine kinase is a regulatory site. To investigate directly the ability of tyrosine phosphorylation to affect P130gag--fps kinase activity, the phosphotyrosyl phosphatase inhibitor orthovanadate and partially purified phosphotyrosyl phosphatases were used to manipulate the stoichiometry of P130gag--fps phosphorylation. Phosphorylation of P130gag--fps at Tyr 1073 correlated with enhanced kinase activity. The thermolabile phosphorylation, kinase activity and transforming ability of P140gag--fps encoded by a temperature-sensitive (ts)FSV variant were restored at the non-permissive temperature for transformation by incubation of infected cells with orthovanadate. In this case tyrosine phosphorylation can apparently functionally reactivate a conditionally defective v-fps kinase activity. These data suggest that reversible autophosphorylation at a conserved tyrosine within the v-fps kinase domain is a positive regulator of enzymatic activity and biological function. Phenotypic suppression of the tsFSV genetic defect by orthovanadate emphasizes the potential importance of phosphotyrosyl phosphatases in antagonizing tyrosine kinase action. It is suggested that autophosphorylation may constitute a molecular switch by which some protein-tyrosine kinases are activated.
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PMID:Enzymatic activation of Fujinami sarcoma virus gag-fps transforming proteins by autophosphorylation at tyrosine. 303 4

We have isolated a human genomic DNA (designated human frt) cross-hybridizing with the v-ros oncogene of UR2 sarcoma virus. Sequencing analysis of this fragment revealed that this sequence contains a 123-base-pair exon-like structure surrounded by consensus sequences of splice acceptor and donor sites. The deduced amino acid sequence of this stretch was highly homologous to a portion of a tyrosine kinase domain of src family. The human frt sequence was found to be conserved in a wide variety of vertebrates. By using a human-mouse hybridoma panel, human frt was located on chromosome 13, while human c-ros-1 was located on chromosome 6.
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PMID:A possible new member of tyrosine kinase family, human frt sequence, is highly conserved in vertebrates and located on human chromosome 13. 304 Jun 50

An increasing number of polypeptide growth factors have been identified that regulate not only cell proliferation but an extraordinary range of cell activities, including matrix protein deposition and resolution, the maintenance of cell viability, cell differentiation, inflammation, and tissue repair. Normal cells appear to require growth factors for proliferation and for maintenance of viability. Cells that secrete a polypeptide growth factor have an advantage in growth. These factors can act either externally through cell surface receptors or perhaps internally during the transport of receptors and growth factors through the ER and Golgi, causing autocrine stimulation of cell growth. Depending on the cell type, growth factors can also be potent inhibitors of cell growth rather than stimulating growth, and the effects can depend on the presence or absence of other growth factors. Platelet-derived growth factor has been shown to be nearly identical to the product of the v-sis gene of the simian sarcoma virus, which appears to cause cell transformation through its interactions with the PDGF receptor activating the tyrosine kinase activity of the PDGF receptor. Similarly, two proto-oncogenes, c-erbB and c-fms, encode growth factor receptors. The EGF receptor activity of the v-erb oncogene product appears to be constitutively activated without the need for growth factor, perhaps because of the truncation at the amino terminus deleting the EGF binding domain. The induction of the myc and the fos proteins by growth factor stimulation of quiescent cells, as well as the potential for the p21 product of the ras oncogene to act as an intermediate in transducing adrenergic signals, provide direct evidence that these pathways are important for stimulation of cell growth. Cells transformed by the v-sis oncogene always appear to bear PDGF cell surface receptors, which suggests that this oncogene has a specific requirement of the PDGF receptor for transformation. In contrast, cells transformed by the v-erbB and v-fms oncogenes are not stimulated by EGF or by CSF-1. Thus it seems likely that the tyrosine kinase activity of the corresponding receptor is ubiquitously expressed in these cases. Major questions remain unanswered. In particular, what are the mechanisms by which growth factors initiate pathways leading to DNA synthesis? What are the physiological substrates of the growth factor receptor tyrosine kinase? Considerable effort also is needed to further define the cellular specificity of the different growth factors, particularly within intact tissues, and to determine how the various growth factors interact.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Polypeptide growth factors: roles in normal and abnormal cell growth. 331 82


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