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Query: UNIPROT:P06889 (Mol)
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The c-src protein isolated from neuronal cells (pp60c-src+) displays a higher level of protein kinase activity than does pp60c-src from nonneural tissues. There are two structural alterations present in the amino-terminal half of pp60c-src+ expressed in neurons which could contribute to the enhanced activity of this form of pp60c-src: (i) a hexapeptide insert located at amino acid 114 of avian pp60c-src+ and (ii) a novel site(s) of serine phosphorylation. We characterized pp60c-src+ expressed in a nonneuronal cell type to identify factors that regulate the activity of the c-src+ protein and the importance of the neuronal environment on this regulation. The c-src+ protein overexpressed in chicken embryo fibroblasts (CEFs) displayed higher kinase activity than did pp60c-src. The major sites of phosphorylation of the c-src+ protein were Ser-17 and Tyr-527. The unique site(s) of serine phosphorylation originally identified in pp60c-src+ expressed in neurons was not detected in the c-src+ protein overexpressed in CEFs. Therefore, the hexapeptide insert is sufficient to cause an elevation in the tyrosine protein kinase activity of pp60c-src+. Our data also indicate that CEFs infected with the Rous sarcoma virus (RSV)c-src+ display phenotypic changes that distinguish them from cultures producing pp60c-src and that pp60c-src+-expressing cells are better able to grow in an anchorage-independent manner. The level of total cellular tyrosine phosphorylation in RSVc-src+-infected cultures was moderately higher than the level observed in cultures infected with RSVc-src. This level was not as pronounced as that observed in cells infected with RSVv-src or oncogenic variants of RSVc-src. Thus, pp60c-src+ could be considered a partially activated c-src variant protein much like other c-src proteins that contain mutations in the amino-terminal domain.
Mol Cell Biol 1989 Aug
PMID:Biological and biochemical properties of the c-src+ gene product overexpressed in chicken embryo fibroblasts. 247 84

Cyclic AMP stimulates transcription of the genes encoding the alpha- and beta-subunits of human CG (hCG). Although the cis-acting cAMP response element (CRE) of the alpha-subunit gene has been extensively characterized, relatively little is known about the putative response element of the hCG beta gene. Here, we demonstrate that cAMP stimulation of hCG beta gene transcription requires ongoing protein synthesis, whereas cAMP stimulation of alpha-subunit gene transcription does not. These results suggest that cAMP-stimulated transcription of the alpha and hCG beta genes may involve different cis-acting elements and trans-acting factors. Accordingly, we have constructed a series of deletion mutants consisting of fragments of the hCG beta promoter-regulatory region linked to the bacterial chloramphenicol acetyl transferase gene. To potentiate detection of a CRE, we constructed vectors containing the Rous sarcoma virus enhancer to augment transcriptional activity of the hCG beta-promoter. We also used vectors designed to determine whether regions containing a putative CG beta CRE could confer cAMP responsiveness to a heterologous promoter. These constructs were evaluated for activity by transfection into choriocarcinoma (BeWo) cells. Transient expression of these vectors identifies a broad region which renders transcription of the chloramphenicol acetyl transferase gene responsive to cAMP. Surprisingly, division of the hCG beta 5'-flanking and untranslated regions into smaller fragments led to loss of cAMP responsiveness, suggesting that the hCG beta CRE may be comprised of multiple domains dispersed across the proximal 650 base pairs of CG beta 5'-flanking and untranslated sequence.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Jul
PMID:The transcriptional response of the human chorionic gonadotropin beta-subunit gene to cAMP is cycloheximide sensitive and is mediated by cis-acting sequences different from that found in the alpha-subunit gene. 247 92

Immunoprecipitates of p60v-src proteins from chicken embryo fibroblasts infected with Rous sarcoma virus were assayed for phosphatidylinositol (PI) kinase activity in the absence of detergents. The product of the PI kinase reaction, phosphatidylinositol monophosphate (PIP), migrated slightly slower than did the authentic phosphatidylinositol-4-monophosphate marker in thin-layer chromatography and was indistinguishable from phosphatidylinositol-3-monophosphate produced by PI kinase type I. Furthermore, the deacylated product comigrated with glycerophosphoinositol-3-phosphate in high-performance liquid chromatography. Both sucrose gradient fractionation and the heat stability of PI kinase activity from cells infected with temperature-sensitive mutants suggest that the PI kinase activity is not intrinsic to p60v-src but is a property of another molecule complexed with p60v-src. All transforming variants of p60src were associated with PI kinase activity, whereas this enzyme activity was hardly detectable in immunoprecipitates from cells infected with nontransforming viruses encoding p60c-src or an enzymatically inactive variant. However, PI kinase activity was found in p60src immunoprecipitates from cells infected with nonmyristylated, nontransforming mutants as well as temperature-sensitive mutants at the nonpermissive temperature, which indicated that simple association of PI kinase activity with p60src is not sufficient for cell transformation.
Mol Cell Biol 1989 Apr
PMID:Phosphatidylinositol kinase activity associates with viral p60src protein. 254 73

The internal enhancer binding factor (IBF) that specifically binds sequences within the gag gene internal enhancer of Rous sarcoma virus Schmidt-Ruppin A was purified to near homogeneity from BHK cells. The polypeptides that constituted IBF DNA-binding activity were identified by sodium dodecyl sulfate-polyacrylamide gel analysis. As isolated from BHK cells, IBF consisted of two different but related polypeptides. One (IBF alpha) had a molecular weight of 40,000; the other (IBF beta) had a molecular weight of 20,000 and appeared to be a proteolytic product of IBF alpha. The site within the gag gene to which IBF bounds in vitro (internal enhancer site 2; nucleotides 856 to 878 of the Rous sarcoma virus genome) were demonstrated to function as a cis-acting transcriptional stimulatory element both in vivo and in vitro. By using HeLa cell nuclear transcription extracts, purified IBF was found to function as a trans-acting transcription factor that stimulated transcription in vitro. Purified IBF was also demonstrated to be very similar to EBP20 (K. Carlberg, T. A. Ryden, and K. Beemon, J. Virol. 62:1617-1624, 1988), and it may well belong to the same family of DNA-binding proteins.
Mol Cell Biol 1989 May
PMID:Purification and properties of the Rous sarcoma virus internal enhancer binding factor. 254 54

The structure of provirus in Syrian hamster cells, transformed by Rous sarcoma virus (RSV) varying in metastatic capability in vivo has been analysed. The original cell line and its low metastatic variants contain only one copy of the integrated RSV genome. The DNA of highly metastatic cell lines cloned from the same primary culture, contain an additional copy of provirus. This RSV copy in different highly metastatic variants has a similar integration site.
Mol Biol (Mosk)
PMID:[Differences in the distribution of proviruses in low- and highly- metastatic variants of hamster cells, transformed by Rous sarcoma virus]. 254 1

Novel antibodies were raised against a synthetic NH2-terminal myristoyl(Myr-) tetrapeptide(N-Myr-Gly-Ser-Ser-Lys) which is characteristic of an NH2-terminal portion of pp60v-src, the transforming protein of Rous sarcoma virus. Antisera raised against N-Myr-Gly-Ser-Ser-Lys-haemocyanin reacted with 125I-albumin conjugates with N-Myr-Gly-Ser-Ser-Lys. The immunoreaction was competed for by haemocyanin as well as albumin conjugated with this N-Myr-peptide, while underivatized proteins or an NH2-terminal octapeptide (Gly-Ser-Ser-Lys-Ser-Lys-Pro-Lys) had no effect. N-Myr-Gly-Ser-Ser-Lys-(125I)tyramine was also recognized by the antibody. The reaction was competed for by N-Myr-Gly-Ser-Ser-Lys, but not by Gly-Ser-Ser-Lys-Ser-Lys-Pro-Lys. These results suggest a high affinity of the antibody for an N-Myr-peptide moiety. The major (3H)myristate-labelled protein of an apparent molecular weight of 60,000 was detected from chick embryo fibroblasts transformed by Rous sarcoma virus (tsNY68). This protein was demonstrated to possess N-Myr-Gly-Ser-Ser-Lys by the immunoprecipitation and HPLC analyses. Furthermore, the entire circumference of the transformed cells was stained by the antibody upon an immunofluorescent microscopic observation. Thus, these results taken together indicate that the haptenic antibody raised against the myristoyl peptide is useful to detect pp60v-src protein.
Mol Cell Probes 1989 Sep
PMID:A novel antibody against a synthetic NH2-terminal myristoyl glycyl src peptide can detect pp60v-src, the transforming protein of Rous sarcoma virus. 255 99

We studied the expression of 9E3 mRNA, which is known to be induced in chicken embryo fibroblasts by p60v-src activity and by serum. In addition to full-length 9E3 mRNA, we identified several smaller RNAs that hybridized with 9E3 cDNA. One of these RNAs hybridized with a 5' 9E3 cDNA probe but not with a 3' cDNA probe. The other hybridized with a 3' cDNA probe but lacked 5' sequences, including the entire 9E3 coding region. Only the latter RNA was polyadenylylated, as determined by RNase H digestion in the presence of oligo(dT). The level of the small RNAs increased after treatment with cycloheximide and actinomycin D, indicating that the small RNAs were produced by processing of preexisting transcripts. The derivation of the small RNAs from 9E3 mRNA rather than from a related gene was confirmed by S1 nuclease analysis. The 3' terminus of the 5' RNA and the 5' terminus of the 3' RNA mapped to the same position, which suggested that the small RNAs were formed by endonucleolytic cleavage of 9E3 mRNA at a specific site in the 3' noncoding region. We also found that the stability of 9E3 mRNA was increased after serum stimulation and was greater in Rous sarcoma virus-transformed than in uninfected cells. The relative amount of the small RNAs as compared with the full-length transcript was greatest under conditions in which the full-length transcript was least stable. These data suggest that site-specific endonucleolytic cleavage regulates the stability of 9E3 mRNA.
Mol Cell Biol 1989 Nov
PMID:Processing of 9E3 mRNA and regulation of its stability in normal and Rous sarcoma virus-transformed cells. 255 39

For the elucidation of the molecular basis of RSV adaptation to conditionally permissive host from the genome library of duck embryo fibroblasts, transformed by Rous sarcoma virus in 30 passages on these cells, recombinant bacteriophages that include provirus sequences, were obtained. Complete and transformation-defective proviruses were characterized, nucleotide sequences of their env-genes were compared with their counterparts the original RSV (Pr-RSV-C) and with viruses of other subgroups (A, B, D and E). The possible relation of the revealed changes in domains coding gp85 and gp37, with the changes of chicken RSV characteristics during adaptation to duck cells is discussed.
Mol Biol (Mosk)
PMID:[The family of env genes of avian retroviruses: molecular analysis of Rous sarcoma virus adapted to duck cells]. 255 92

Transfection of cultured cells with functioning foreign genes can be a powerful tool for delineating mechanisms controlling gene expression and for manipulating cellular synthetic machinery. We transfected cultured bovine pulmonary artery endothelial cells with a plasmid (pRSVCAT) containing the prokaryotic gene, chloramphenicol acetyltransferase (CAT), driven by a Rous sarcoma virus (RSV) promoter. Transfection was accomplished by binding the plasmid DNA to specially synthesized cationic liposomes and incubating cell monolayers with the liposome-DNA complex (a process called lipofection). We found marked CAT expression in endothelial cells by 24 h after lipofection (complete chloramphenicol acetylation in a 4-h assay incubation with less than 0.1 mg cell protein). Marked CAT expression persisted after splitting the cells 1:2 at 6 days after lipofection. Detectable CAT activity was present 14 days after lipofection following two 1:2 splits of the cells. CAT expression was related to the quantity of plasmid DNA used for lipofection; 1.0 micrograms DNA per 60-mm dish of cells resulted in less CAT activity at 48 h than did 5 or 10 micrograms DNA per dish. Ten micrograms of DNA-liposome complex per dish caused substantial numbers of endothelial cells to detach from the dish, but little cytotoxic effect was seen with 5 or 1 micrograms DNA-liposome complex per dish. This simple, highly efficient method for introducing functioning foreign genes into cultured endothelial cells will permit a broad range of studies of molecular mechanisms of endothelial cell function and studies of the consequences of highly specific modifications in protein synthesis on endothelial responses.
Am J Respir Cell Mol Biol 1989 Aug
PMID:Expression of a prokaryotic gene in cultured lung endothelial cells after lipofection with a plasmid vector. 255 63

The oncogene (v-src) of Rous sarcoma virus apparently arose by transduction of the chicken gene known as c-src(chicken). We isolated DNA fragments representative of two src-related loci from recombinant DNA bacteriophage libraries of the human genome. One of these loci, c-src1(human), appeared to direct the synthesis of a 5-kilobase polyadenylated RNA that presumably encodes pp60c-src(human). Probes specific for the other locus, c-src2(human), did not hybridize to polyadenylated RNA prepared from a variety of human cell lines. Partial nucleotide sequence determinations of the loci demonstrated that c-src1(human) is highly related to chicken c-src and that c-src2(human) is slightly more divergent. The sequences imply that the final two coding exons of each human locus are identical in length to those of chicken c-src and that the location of an amber stop codon is unchanged in all three loci. c-src1(human) has been mapped to chromosome 20, and the second locus is located on chromosome 1. We conclude that c-src1(human) is the analog of c-src(chicken) and that the duplicated locus, c-src2(human), may also be expressed.
Mol Cell Biol 1985 Apr
PMID:Isolation of duplicated human c-src genes located on chromosomes 1 and 20. 258 Nov 27


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