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

The v-vis gene encodes p28sis, the transforming protein of simian sarcoma virus. This gene resulted from a fusion of the env gene of simian sarcoma-associated virus and the woolly monkey gene for the B chain of platelet-derived growth factor (PDGF). Previous work has shown that the v-sis gene product undergoes signal sequence cleavage, glycosylation, dimerization, and proteolytic processing to yield a secreted form of the protein. It transport across the endoplasmic reticulum is blocked by the introduction of a charged amino acid residue within the signal sequence, the protein does not dimerize, is not secreted, and is no longer transforming as assayed by focus-forming ability in NIH 3T3 cells. Instead, this mutant protein localizes to the nucleus as demonstrated by both indirect immunofluorescence and cell fractionation. Using a series of deletion mutations, we delimited an amino acid sequence within this protein which is responsible for nuclear localization. This region is completely conserved in the predicted human c-sis protein, although it lies outside of regions required for transformation by the v-sis gene product. This nuclear transport signal is contained within amino acid residues 237 to 255, RVTIRTVRVRRPPKGKHRK. An amino acid sequence containing these residues is capable of directing cytoplasmic v-sis mutant proteins to the nucleus. This sequence is also capable of directing less efficient nuclear transport of a normally cytoplasmic protein, pyruvate kinase. Pulse-chase experiments indicate that the half-lives of nuclear and cytoplasmic v-sis mutant proteins are approximately 35 min. Using the heat-inducible hsp70 promoter from Drosophila melanogaster, we showed that the nuclear v-sis protein accumulates in the nucleus within 30 min of induction. The identification of a nuclear transport signal in the v-sis gene product raises interesting questions regarding the possibility of some function for PDGF or PDGF-related molecules in the nucleus.
Mol Cell Biol 1987 Oct
PMID:Identification of a signal for nuclear targeting in platelet-derived-growth-factor-related molecules. 331 80

The autocrine effects of platelet-derived growth factor (PDGF) A- and B-chain homodimers (PDGF-AA and PDGF-BB) on rat-1 cells and human fibroblasts have been investigated by using human PDGF A- and B-chain cDNA clones expressed in a retroviral vector. Infection with replication-defective virus carrying the B-chain cDNA resulted in a phenotypical transformation resembling that induced by simian sarcoma virus. The resulting cells were focus forming in monolayer cultures, grew to high saturation densities, and formed large colonies in soft agar. The PDGF A-chain transfectants showed no transformed morphology and lacked focus-forming activity but grew to high saturation density in monolayer culture and formed small colonies in soft agar. A similar but weaker effect was obtained with an A-chain cDNA variant containing a 69-base-pair insertion in the 3' end of the protein-coding domain. A- and B-chain transfectants released PDGF receptor-competing activity into the medium, but only the medium conditioned by the B-chain transfectants possessed potent mitogenic activity on human fibroblasts. Both types of transfectants had downregulated levels of PDGF receptors; however, the B-chain transfectants were downregulated to significantly lower levels. Metabolic labeling and immunoprecipitations with PDGF antiserum showed that the PDGF B-chain protein was processed to a 24-kilodalton cell-associated and a 30-kilodalton secreted dimeric protein. The A-chain protein was rapidly secreted as a 31-kilodalton dimeric protein. The present study shows a marked difference in the autocrine effects of PDGF-AA and -BB expressed under the control of a retroviral promoter and suggests that different biological properties may be assigned to these two PDGF isoforms.
Mol Cell Biol 1988 Jul
PMID:Expression of recombinant platelet-derived growth factor A- and B-chain homodimers in rat-1 cells and human fibroblasts reveals differences in protein processing and autocrine effects. 340 17

Brief digestion of sarcoma-180 chromatin (less than or equal to 5%) by pancreatic DNase-I releases six non-histone proteins with Mol. wt. 21.5K, 26K, 72.5K, 77K, 90K and 120K dalton and pI values ranging from 4.7 to 12.4. The protein of Mol. wt. 77K dalton was obtained at high alkaline range of pH = 12.4. The antibodies against these proteins induce dose dependent inhibition in transcription of native chromatin. Results suggest a role of these proteins in positive control of gene transcription in sarcoma-180 cells.
Mol Cell Biochem 1987 Dec
PMID:Characterization of DNA binding proteins released from sarcoma-180 chromatin during brief digestion with DNase-I. 344 Dec 49

We have compared several recombinant retroviruses carrying the selective marker NeoR for gene delivery to murine haemopoietic stem cells. Provirus content and expression was assessed in animals reconstituted with infected bone marrow cells. With viruses bearing only a NeoR gene, viral RNA was readily detectable both in spleen colonies and in the haemopoietic tissues of long-term reconstituted mice. Thus, the progeny of infected primitive multipotential cells are competent to express integrated proviruses. The level of expression was significantly greater for proviruses carrying a modified long terminal repeat in which the Moloney enhancer had been replaced with that from the myeloproliferative sarcoma virus. With viruses bearing the c-myc gene in addition to NeoR, however, no viral RNA could be detected in spleen colonies harbouring proviral inserts, even though these viruses are expressed in vitro within haemopoietic cells. The implications of these results for gene transfer to haemopoietic stem cells are discussed.
Mol Biol Med 1987 Aug
PMID:Expression of genes transferred to haemopoietic stem cells by recombinant retroviruses. 367 48

A number of deletion mutants were isolated, including 5', 3', and internal deletions in the 5'-flanking region of the human cellular oncogene related to the Harvey sarcoma virus (c-H-ras), and their transforming activities were examined in NIH 3T3 cells. DNA sequences which could not be detected without losing transforming activity were localized to a relatively short stretch upstream of the region which showed homology to the 5'-flanking region of v-H-ras oncogene. S1 nuclease analysis indicated that there were two clusters of mRNA start sites at positions that were about 1,371 and 1,298 base pairs upstream of the first coding ATG. The minimum region required for promoter function was estimated to be a 51-base-pair-long (or less) DNA segment. The promoter was GC rich (78%) and did not contain the consensus sequences that are usually observed in PolII-directed promoters but contained a GC box within which one of the mRNA start sites was included. In addition, two sets of positive and negative elements seemed to be located between the promoter and the protein-coding region, which appeared to influence positively and negatively, respectively, the efficiency of transformation with the c-H-ras oncogene.
Mol Cell Biol 1987 Aug
PMID:Identification of the principal promoter sequence of the c-H-ras transforming oncogene: deletion analysis of the 5'-flanking region by focus formation assay. 367 Mar

A tumor antigen isolated from the cytosol of a methylcholanthrene-induced sarcoma (Meth A) has been purified to homogeneity by the criteria of two-dimensional gel analysis and NH2- and COOH-terminal sequencing. The purified antigen has a mol. wt of 82,000 by SDS gel electrophoresis. However, the apparent mol. mass of the antigen was found to be 71,600 and 67,700 by gel filtration chromatography and sedimentation analysis, respectively. It is not a glycoprotein, possesses an acidic isoelectric point (6.0) and exists as dimeric and monomeric species. The dimer is not held together by disulfide bonds. The purified protein retains its ability to induce transplantation immunity in syngeneic hosts when challenged with Meth A sarcomas. Chemical analyses of the NH2- and COOH-termini gave the following sequences: NH2-PKPINVRVTTMDAELEFAIQPN and IDE(F,A)EM-COOH, respectively.
Mol Immunol 1986 May
PMID:Characterization of a chemically homogeneous tumor antigen from a methylcholanthrene-induced sarcoma, Meth A. 374 14

Marked differences in cardiac associated morbidity and mortality have been reported between patients with and without malnutrition. Tumor-associated cachexia may impair heart function, which further aggravate host wasting and thereby create a vicious circle. The aim of this study was to evaluate to what extent a malignant tumor may influence heart function under well-defined experimental conditions. The perfused working rat heart was used as a model. Study groups of freely-fed sarcoma-bearing rats, starved and protein-calorie malnourished (PCM) non-tumor rats were compared to freely-fed control animals. All groups of malnourished animals (tumor-bearing, starved and PCM) lost significant amounts of body and heart mass compared to freely-fed controls. Loss of heart contractile mass in tumor-bearing rats and malnourished animals did not lead to impaired heart function in any respect. The rate of oxygen uptake was significantly higher under all experimental conditions in perfused hearts from tumor-bearing rats compared with hearts from starved, PCM and freely-fed control rats. Oxygen uptake per left ventricular work was significantly higher in tumor-bearing rats but significantly lower in starved and PCM rats compared with control animals. Norepinephrine at various concentrations (10(-9)-10(-5) mol/l) in the perfusate stimulated the contractility and the left ventricular peak pressure significantly more in hearts from malnourished animals compared with that of freely-fed controls. The results show that adaptive functional changes can be recorded in the isolated perfused rat heart from sarcoma-bearing rats and after a period of comparatively acute undernutrition in non-tumor rats. A malignant tumor or the associated malnutrition does not induce impaired pumping performance despite a reduction in contractile heart mass. Increased oxygen consumption in hearts from tumor-bearing animals may contribute to elevated energy expenditure in a cancer-bearing host.
J Mol Cell Cardiol 1986 Nov
PMID:Effects of tumor-load and malnutrition on myocardial function in the isolated working rat heart. 379 77

Mouse hepatoma-rat hepatocyte hybrids that segregate rat chromosomes were used to determine the chromosomal localization of rat cellular RAS genes. The cellular KRAS gene, homologous to the Kirsten sarcoma virus oncogene was mapped to rat chromosome 4, a chromosome that is often present in three copies in rat neurogenic tumor cells and transformed glial cells. The rat cellular HRAS-1 gene, homologous to the Harvey sarcoma virus oncogene was assigned to chromosome 1, whereas its intron-less counterpart HRAS-2 was mapped to the X chromosome. Since the human HRAS-2 also resides on the X chromosome, it appears that the cellular HRAS-2 gene (or pseudogene) conserved its chromosomal localization during mammalian evolution.
Somat Cell Mol Genet 1985 Jan
PMID:Assignment of three rat cellular RAS oncogenes to chromosomes 1, 4, and X. 385 33

The human germ-line position of c-erb-A, the cellular counterpart of v-erb-A, has been determined by in situ molecular hybridization of a 3H-labeled c-onc gene probe to meiotic pachytene chromosomes. Both v-erb-A and v-erb-B are the v-onc genes that are associated with induction of sarcoma and erythroblastosis in chicken by the avian erythroblastosis virus, a rapidly transforming RNA tumor virus. The position of c-erb-A, determined here to be at 17q21.33-q22, is in the same region of chromosome 17 in which a nonrandom break occurs in the generation of t(15;17), a translocation commonly seen in acute promyelocytic leukemia.
Somat Cell Mol Genet 1985 Jan
PMID:Germ-line chromosomal localization of human C-Erb-A oncogene. 385 34

Cells transformed by Harvey or Moloney sarcoma virus secrete at least 40 times as much type beta transforming growth factor as their respective untransformed control cells. The transformed cells bind only 20 to 50% as much type beta transforming growth factor as the control cells, suggesting that transformation causes down-regulation of the type beta transforming growth factor receptor.
Mol Cell Biol 1985 Jan
PMID:Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. 385 35


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