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

Proteins encoded by oncogenes such as v-fps/fes, v-src, v-yes, v-abl, and v-fgr are cytoplasmic protein tyrosine kinases which, unlike transmembrane receptors, are localized to the inside of the cell. These proteins possess two contiguous regions of sequence identity: a C-terminal catalytic domain of 260 residues with homology to other tyrosine-specific and serine-threonine-specific protein kinases, and a unique domain of approximately 100 residues which is located N terminal to the kinase region and is absent from kinases that span the plasma membrane. In-frame linker insertion mutations in Fujinami avian sarcoma virus which introduced dipeptide insertions into the most stringently conserved segment of this N-terminal domain in P130gag-fps impaired the ability of Fujinami avian sarcoma virus to transform rat-2 cells. The P130gag-fps proteins encoded by these transformation-defective mutants were deficient in protein-tyrosine kinase activity in rat cells. However v-fps polypeptides derived from the mutant Fujinami avian sarcoma virus genomes and expressed in Escherichia coli as trpE-v-fps fusion proteins displayed essentially wild-type enzymatic activity, even though they contained the mutated sites. Deletion of the N-terminal domain from wild-type and mutant v-fps bacterial proteins had little effect on autophosphorylating activity. The conserved N-terminal domain of P130gag-fps is therefore not required for catalytic activity, but can profoundly influence the adjacent kinase region. The presence of this noncatalytic domain in all known cytoplasmic tyrosine kinases of higher and lower eucaryotes argues for an important biological function. The relative inactivity of the mutant proteins in rat-2 cells compared with bacteria suggests that the noncatalytic domain may direct specific interactions of the enzymatic region with cellular components that regulate or mediate tyrosine kinase function.
Mol Cell Biol 1986 Dec
PMID:A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps. 302 55

The in vitro expression of two distinct proteins from overlapping reading frames in a sequence of rainbow trout genomic DNA has been demonstrated. In vitro transcription of DNA sequences, cloned in a plasmid under the control of Salmonella phage 6 polymerase promoter, led to the synthesis of two distinct and functional mRNAs corresponding to the protamine mRNA and also to another overlapping mRNA, termed Y. These mRNAs were translated in an mRNA-dependent rabbit reticulocyte lysate cell free system which synthesized the corresponding protein products. Similarities between the synthesized Pro-rich protein Y and three proline-rich proteins, the human salivary Pro-rich protein, the avian sarcoma virus protein P19 and the myc oncogene product, were evident and the significance of these findings is discussed. A synthetic oligonucleotide which is complementary to a sequence corresponding to a region of the Y protein mRNA, but upstream (5') of the transcribed protamine mRNA, hybridized faintly and only to trout brain RNA. However, more sensitive primer extension studies utilizing the Y-specific oligonucleotide detected several Y-related mRNAs in trout brain.
J Mol Evol 1986
PMID:In vitro expression of two proteins from overlapping reading frames in a eukaryotic DNA sequence. 303 20

Newly isolated strains of avian sarcoma virus, S1 and S2, were shown to have the transduced cellular src gene as their viral transforming gene (Yamagishi et al., Virology 137:266-275, 1984). In this work, the S1 and S2 genomes were molecularly cloned, and the junction sequences between the viral genomes and the c-src genes and the complete nucleotide sequences of the v-src genes transduced in these viruses were determined. Data on the junction sequences suggested that 5' recombination had occurred between the 5'-noncoding region of c-src and the 5' region of the gag sequence encoding p19 in both viruses and that 3' recombination had occurred in the last coding exon of c-src with either the middle portion of the env sequence encoding gp85 for S1 or the 3' portion of pol coding for reverse transcriptase for S2. Comparison of the amino acid sequences of the S1 and S2 src products deduced from the nucleotide sequences (pp62S1-src and pp62S2-src with that of c-src protein (pp60c-src) indicated that in pp62S1-src the 8 carboxy-terminal amino acid residues of the total of 533 in pp60c-src are replaced by 43 residues translated from the env sequence at the wrong frame. In pp62S2-src, on the other hand, the 14 carboxy-terminal amino acids of pp60c-src are replaced by the 38 carboxy-terminal residues of reverse transcriptase. The mechanism of c-src transduction and the structural changes necessary for pp60c-src activation are discussed.
Mol Cell Biol 1986 Jul
PMID:Activation of the cellular src gene by transducing retrovirus. 309 13

We describe the characteristics of a repetitive DNA sequence from the rainbow trout and related salmonid fishes that is similar to a retroviral long terminal repeat (LTR). The repeat is 160 bp long and contains a region of homology to the LTR of the avian sarcoma virus. Two clones with this repeat from the chum salmon also have a polypurine tract and tRNA binding site, respectively, and these clones may represent the two LTRs of a retrovirus or retroviral-like repetitive element. Copies of the repeat are also adjacent to rainbow trout and chum salmon protamine genes. These repeats may be "solo" LTRs. There appears to be some polymorphism in restriction sites between individual rainbow trout and considerable differences between salmonid fish species when the repeat is used as a probe.
J Mol Evol 1988
PMID:A repetitive DNA sequence in the salmonid fishes similar to a retroviral long terminal repeat. 313 84

We isolated molecular clones of chicken DNA that carry portions of the cellular proto-oncogene c-fps and then determined the nucleotide sequence of all regions of the gene that are related to the retroviral oncogene v-fps. The homology of v-fps within c-fps resides on at least 19 interspersed segments, 17 of which represent complete exons and two of which may represent only portions of exons. Fusion of these segments reconstructs a facsimile of v-fps. The arrangement of introns and exons within c-fps differs from that of the related proto-oncogene c-src in the domains of the two genes that encode tyrosine-specific protein kinase activity. It therefore appears likely that the introns arose subsequent to the gene duplication that engendered c-src and c-fps. The data also reveal potential junctions between viral and cellular domains in the genomes of two independently isolated avian sarcoma viruses (the PRCII and Fujinami strains). The lefthand junctions can be well defined: they occur at the same position in c-fps but at different positions in the viral gene gag. The righthand junctions cannot be defined as precisely because they include a sequence of 10 to 15 nucleotides whose origin is not known. In the genome of PRCII virus, the composition of this sequence suggests that it arose from the polyadenylated 3' terminus of the c-fps messenger RNA. If this deduction proves to be correct, the data will provide direct evidence that the righthand recombination during transduction by retroviruses occurs between RNA intermediates. Irrespective of these ambiguities, both junctions are located within exons of c-fps, and both may have been formed by non-homologous recombination (although the evidence for the latter statement is not decisive). A sequence of 1020 nucleotides has been deleted from the transduced version of c-fps in the genome of PRCII virus, apparently by homologous recombination between sequences repeated within c-fps. Fujinami virus may contain the entire coding domain of c-fps, but mutations have created 26 amino acid substitutions in the viral version of the gene. By contrast, the partially deleted version of c-fps in PRCII virus contains no mutations that would alter the amino acid sequence.
J Mol Biol 1985 Jan 20
PMID:Nucleotide sequence and topography of chicken c-fps. Genesis of a retroviral oncogene encoding a tyrosine-specific protein kinase. 387 69

Studies on ts mutants of avian sarcoma viruses have previously implicated the src gene product (pp60src) kinase function in in vitro transformation. The role of src in vivo, however, has not been clearly defined. Using a sensitive and quantitative assay that was developed in chicken embryos (Chambers et al., Cancer Res. 42:4018-4025, 1982), we tested the in vivo tumorigenic properties of cells transformed with LA23, an avian sarcoma virus that is temperature sensitive for in vitro transformation. We found that the in vivo growth ability of these cells was temperature sensitive and that this in vivo behavior correlated with the in vitro transformation behavior (growth in soft agar and saturation density).
Mol Cell Biol 1985 Apr
PMID:Cells transformed with a ts viral src mutant are temperature sensitive for in vivo growth. 392 24

Murine 3T3L1 preadipocytes transformed by avian sarcoma virus were unable to differentiate in response to insulin or dexamethasone plus 1-methyl-3-isobutylxanthine, both potent inducers of differentiation of the nontransformed 3T3L1 parental line. Conditioned medium from transformed cells contained a relatively heat-stable factor(s) which inhibited the differentiation of untransformed parental 3T3L1 cells but did not induce any changes in their morphology. A protease-sensitive mitogen was also detected in the medium. The relationship between the two activities remains to be elucidated.
Mol Cell Biol 1985 Oct
PMID:v-src inhibits differentiation via an extracellular intermediate(s). 393 55

Chicken embryo cells transformed by the related avian sarcoma viruses PRC II and Fujinami sarcoma virus, or by the unrelated virus Y73, contain three phosphoproteins not observed in untransformed cells and increased levels of up to four other phosphoproteins. These same phosphoproteins are present in increased levels in cells transformed by Rous sarcoma virus, a virus which is apparently unrelated to the three aforementioned viruses. In all cases, the phosphoproteins contain phosphotyrosine and thus may be substrates for the tyrosine-specific protein kinases encoded by these viruses. In one case, the site(s) of tyrosine phosphorylation within the protein is the same for all four viruses. A homologous protein is also phosphorylated, at the same major site, in mouse 3T3 cells transformed by Rous sarcoma virus or by the further unrelated virus Abelson murine leukemia virus. A second phosphotyrosine-containing protein has been detected in both Rous sarcoma virus and Abelson murine leukemia virus-transformed 3T3 cells, but was absent from normal 3T3 cells and 3T3 cells transformed by various other viruses. We conclude that representatives of four apparently unrelated classes of transforming retroviruses all induce the phosphorylation of tyrosines present in the same set of cellular proteins.
Mol Cell Biol 1981 May
PMID:Four different classes of retroviruses induce phosphorylation of tyrosines present in similar cellular proteins. 608 11

We prepared infectious stocks of an avian retrovirus, a modified spleen necrosis virus, containing the herpes simplex virus type 1 thymidine kinase gene and the avian sarcoma virus v-src gene. Viruses were recovered after cotransfection of chicken cells with DNA of recombinants between cloned spleen necrosis virus thymidine kinase and v-src and with DNA of cloned reticuloendotheliosis virus strain A. When v-src was inserted near the 5'end of the viral genome, only low titers of recombinant virus were recovered. Most of the recovered viruses were smaller than expected and did not transform the morphology of rat or chicken cells. A very small amount of virus of the expected structure was recovered; this virus transformed rat cells and expressed v-src. Cotransfection data indicated that one reason we failed to recover a significant titer of recombinant virus is that efficient expression of v-src is acutely toxic to chicken and dog cells. Insertion of v-src near the 3' end of the viral genome, such that it was expressed at a lower level compared with the 5'-v-src-containing virus, yielded a higher titer of recombinant virus, and this virus was transforming. The differences in the recovery and transforming activity of these viruses indicate that the location of an oncogene in the viral genome is an important factor regulating the level of its expression and whether or not this expression is toxic or transforming to cells.
Mol Cell Biol 1984 Dec
PMID:The location of v-src in a retrovirus vector determines whether the virus is toxic or transforming. 609 17

Normal fibroblasts of the vole displayed moderately spread or flattened, spindle-shaped, or polygonal morphologies and attached firmly to a substrate. Topographic features of these cells included sparse microvilli, ruffles, and filopodia. Microfilament bundles, intermediate filaments, and long microtubules generally parallel to each other, and the long axis of the cell or its extensions were present in the cytoplasm. Fibronectin was abundant, and fibronectin fibrils often formed junctions at the cell membrane with microfilament bundles. Transformation with avian sarcoma virus converted 90% of the cells to spheres 5 to 10 microns in diameter. In contrast to the normal vole cells, microfilament bundles were absent, microtubules were short and randomly arranged, and fibronectin was no longer visible. Exposure to dibutyryl cyclic AMP and testololactone caused a majority of the spherical cells to stretch and flatten, a process referred to as reverse transformation. Microtubules radiated out to the cell periphery and became parallel in cell extensions, while long microfilament bundles appeared in the cytoplasm. Parallel intermediate filaments were arranged throughout the cell. This ultrastructural analysis of reverse transformation in avian sarcoma virus-transformed vole cells detailed the status of the cytoskeletal system and showed agreement with earlier findings (Puck et al., J. Cell. Physiol. 107:399-412, 1981) using indirect immunofluorescence.
Mol Cell Biol 1982 Jul
PMID:Morphological evidence for cyclic AMP-induced reverse transformation in vole cells infected with avian sarcoma virus. 610 Sep 14


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