Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polypeptide sequence of the v-sis transforming gene product of simian sarcoma virus (SSV) can be divided into four regions that are likely to represent structural domains of the protein. Mutations were generated in the SSV nucleotide sequence to assay the extent or function of each of these regions. The results indicate that the helper virus-derived amino-terminal sequence as well as a core region homologous to polypeptide chain 2 of platelet-derived growth factor (PDGF) are required for the transforming function of the protein. Products of transforming but not nontransforming mutants formed dimer structures conformationally analogous to biologically active PDGF.
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PMID:In vitro mutagenesis of the v-sis transforming gene defines functional domains of its growth factor-related product. 299 16

The v-sis transforming gene encodes the woolly monkey homologue of human platelet-derived growth factor (PDGF) polypeptide 2. After its synthesis on membrane bound polyribosomes, the glycosylated precursor dimerizes in the endoplasmic reticulum and travels through the Golgi apparatus. At the cell periphery, the precursor is processed to yield a dimer structurally analogous to biologically active PDGF. Small amounts of two incompletely processed forms are detectable in tissue culture fluids of simian sarcoma virus (SSV) transformants. However, the vast majority remains cell associated. Thus, this growth factor-related transforming gene product is not a classical secretory protein. These findings define possible cellular locations where the transforming activity of the sis-PDGF-2 protein may be exerted.
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PMID:The v-sis/PDGF-2 transforming gene product localizes to cell membranes but is not a secretory protein. 299 41

Estimation of a content of secondary structures from amino acid composition of IL-2 (TCGF), PDGF and transforming protein p28sis of simian sarcoma virus by means of the previously suggested nomograms (V.P. Zav'yalov and A.I. Denesyuk (1982) Immunol. Lett. 4, 7-14) allowed us to conclude that a dominant secondary structure of these proteins should be alpha-helix. Its content in PDGF and p28sis was estimated to be approximately equal to 50%, and that in IL-2 to be 50-65%. The content of beta-pleated structure in PDGF and p28sis does not exceed 10%, and that in IL-2 is found to be 20-30%. In all the proteins investigated five alpha-helical segments can be distinguished, of which one of the surfaces contains clusters of bulky hydrophobic side chains. As the number of alpha-helical segments satisfying the principles of packing into a hydrophobic core as well as the overall length of a polypeptide chain of IL-2 and PDGF coincided with those for IFNs, it was decided to arrange alpha-helices of these proteins into a globular structure by analogy with IFNs (V.P. Zav'yalov and A.I. Denesyuk (1984) Doklady Akad Nauk S.S.S.R. 275, 242-246). In consequence, identical side chains of amino acid residues were found at 9 out of 29 positions in hydrophobic cores of IFN-beta and IL-2, p28sis (PDGF), respectively. Thus the homology of hydrophobic cores of the proteins compared is greater than 30%. Probability of chance coincidences of amino acid residues in the hydrophobic cores of p28sis (PDGF) and IFN-beta is found to be 0.03, and that deduced from comparison of IL-2 and IFN-beta is 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predicted secondary structure and hydrophobic cores of T-cell (TCGF or IL-2) and platelet-derived growth factors as well as of transforming protein p28sis of simian sarcoma virus are similar to those of interferons. 299 60

An immunoblotting procedure using viral proteins from purified murine sarcoma virus or MSV-(MLV) has been developed to characterize antiviral antibodies in sera from patients with autoimmune connective tissue disorders. Fifty-eight sera with anti-Sm, anti-RNP, anti-SS-B (La), and other undefined specificities were found to react with several major viral polypeptide bands. Most of them corresponded to gag-gene-encoded products: pr65gag, p40gag, p30, p15, p12 and p10. Other bands with molecular weights averaging 90K, 60K, 45K, and 28K were recognized by a few sera. Immunological specificity of the reaction was assessed by reproducing the tests with IgG purified from sera and from corresponding F(ab')2 fragments. Moreover, the specificity of the reaction with gag proteins was confirmed by repeating the tests with p30 and p15 prior purified by immunoprecipitation with anti-p30 and anti-p15 goat sera. Furthermore, the gag polypeptides were recognized by human sera by replacing MSV-(MLV) by three other murine retroviruses of different origin. An indirect confirmation of these results was obtained by applying this method to sera of MRL lpr/lpr mice which develop an autoimmune syndrome comparable to that of human systemic lupus erythematosus. In agreement with previously published results (C. Rordorf, C. Gambke, and J. Gordon (1983), J. Immunol. Methods 59, 105-112), we found that anti-gag-gene antibodies were present in the sera of individual mice. Patterns of reactivity were found to vary with the age of the animals. No retroviral polypeptide was significantly detected in the great majority (80%) of sera from normal donors. However, 5 out of 25 sera showed faint bands although to a lesser extent than pathological sera. These five sera also reacted with HeLa cell purified HnRNPs, suggesting that their normal status should be reconsidered.
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PMID:Presence of circulating antibodies against gag-gene MuLV proteins in patients with autoimmune connective tissue disorders. 299 55

The platelet-derived growth factor (PDGF) is a mitogen derived from human platelets consisting of two related polypeptides termed A and B chains. The entire B chain of PDGF is highly (96%) homologous to a portion of p28sis, the transforming protein of simian sarcoma virus. It has been suggested that p28sis exerts its transforming potential by mimicking the growth promoting activity of PDGF and stimulating the cell in an autocrine manner. We have directly examined the mitogenic potential of p28sis and the B chain homologous region by expressing these heterologous sequences in the yeast Saccharomyces cerevisiae. In our constructions, these proteins are encoded by portions of the v-sis gene. Expression and secretion from the yeast cell is achieved by using a yeast promoter and the alpha-factor pheromone secretory leader. The sis proteins thus expressed and secreted are immunoreactive with anti-PDGF antisera and are mitogenic for cultured fibroblasts. Furthermore, they mediate this mitogenic activity by specific binding to the PDGF cell surface receptor. Gel electrophoresis and cell binding analysis indicates that the mitogenic species is primarily a disulphide-bonded dimer. We are able to conclude that p28sis is a mitogen and that a polypeptide corresponding to the B chain alone is sufficient to account for the mitogenic activity attributed to PDGF.
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PMID:The B chain of PDGF alone is sufficient for mitogenesis. 300 57

KNRK cells (a normal rat kidney [NRK] cell line transformed by Kirsten murine sarcoma virus) in sparse culture exhibit a highly ruffled morphology, but the cause of this ruffling is unknown. In this study, we have demonstrated that the continuous, excess ruffling on KNRK cells is caused by one or more soluble agents secreted by the KNRK cells themselves. To do this study, an assay for ruffling responses in live cell cultures was defined, and its reproducibility was demonstrated. This assay permitted observation of the kinetics of ruffling responses (percentage of cells ruffled as a function of time after stimulation). This method was used to compare the kinetics of ruffling induced by insulin, epidermal growth factor, fibroblast growth factor, glucose, and KNRK cell conditioned medium (CM). Ruffling was elicited on NRK cells by each of the polypeptide mitogens and nutrients, but, in each case, this ruffling subsided spontaneously within an hour. CM from KNRK cells also caused ruffling movements on untransformed NRK cells, but this ruffling continued for at least 20 h. This response was largely blocked by premixing the KNRK cell CM with rabbit IgG against rat transforming growth factor, type alpha, (TGF-alpha). KNRK cells made quiescent (ruffle free) by a pH shift (from 7.4 to 8.4) responded to insulin, glucose, and KNRK cell CM with kinetics similar to those observed for each of these factors in NRK cells. The unusual feature for the ruffle-inducing agent(s) produced by KNRK cells was that this activity was not subject, in either NRK or KNRK cells, to the cellular off-regulation that limits the responses to insulin or glucose. Thus, the continuous ruffling of KNRK cells is caused by their own unregulated ruffle-inducing agent or agents, which appear to include TGF-alpha. This work also demonstrates that kinetic analysis of cellular responses to exogenous factors can provide new insights into the regulatory mechanisms involved in the normal limitation of these responses.
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PMID:An agent or agents produced by virus-transformed cells cause unregulated ruffling in untransformed cells. 300 28

A human genomic DNA segment of 5.6 kb containing the entire gene for immune interferon-gamma was fused through its 5'-untranslated region to the corresponding region of the simian virus 40 (SV40) T-antigen gene. The SV40 early promoter used contained a modified transcriptional enhancer element with a 93-bp repeat. Supercoiled plasmid DNA was used to transfect Chinese hamster ovary (CHO) cells, the selectable marker being a SV40-dihydrofolate gene construct. Constitutive expression of the IFN-gamma gene in primary transformants was high, especially if a Harvey murine sarcoma virus long terminal repeat (LTR) was present in addition to the SV40 promoter. After gene amplification by methotrexate selection, CHO-gamma cell lines were obtained that produce 1.5-2 million units of IFN-gamma per million cells and per day (200,000 molecules per cell per minute). Metabolic labeling showed that over 90% of the protein secreted by such cells is human IFN-gamma. A one-step immuno-affinity chromatography on monoclonal antibodies yielded pure IFN-gamma with 1-2 X 10(8) units/mg protein. Like IFN-gamma from human white blood cells, the IFN-gamma from CHO-gamma cells is a mixture of two glycoproteins of 26,000 and 20,000 daltons with traces of the unglycosylated 17,000-dalton polypeptide. Large-scale cultures in 1% serum routinely yield over 600,000 units of human IFN-gamma/ml culture per day.
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PMID:Efficient constitutive production of human IFN-gamma in Chinese hamster ovary cells. 301 45

Cellular transformation of normal rat kidney (NRK) cells by simian sarcoma virus (SSV) results in a complete loss of the cellular requirement of externally added polypeptide growth factors for proliferation. Moreover, SSV-transformed NRK cells have a strongly reduced ability to bind both external platelet-derived growth factor and epidermal growth factor, when compared to nontransformed NRK cells. Analysis of serum-free medium conditioned by SSV-transformed NRK cells shows that this cell line secretes both types alpha and beta transforming growth factor (TGF). The level of TGF alpha production (300 ng/liter conditioned medium) by SSV-transformed NRK is among the highest described to date. Since addition of TGF alpha and beta in combination is sufficient to induce phenotypic transformation of NRK cells, it is concluded that although expression of the sis oncogene is essential for transformation, expression of additional genes may be required for the phenotypic alterations accompanying complete cellular transformation.
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PMID:Production of transforming growth factors by simian sarcoma virus-transformed cells. 302 11

The type, differentiation and histogenesis of the tumor cells of alveolar soft part sarcoma (ASPS) have been analyzed in a series of ten cases by a light-microscopic, ultrastructural, immunohistochemical and cytologic investigation and quantitative DNA analysis. Four tumors deviated from ordinary ASPS: three were wholly or partly of the so-called pleomorphic variant of ASPS and a fourth tumor showed calcifications of the psammoma body type. The ultrastructural findings and immunohistochemical demonstration of desmin supported the hypothesis of a rhabdomyomatous differentiation and gave no support to epithelial (negative immunoreactions for cytokeratins, epithelial membrane antigen, HMFG-1 and -2, tissue polypeptide antigen (TPA] or neuroectodermal (negative for S-100 protein, glial fibrillary acidic protein, neurofilaments) differentiation. The negative immunoreactions for vimentin and myoglobin and the positive reaction for neuron specific enolase (NSE) do not exclude a rhabdomyomatous differentiation since in rhabdomyosarcomas the undifferentiated rhabdomyoblasts generally contain vimentin and the differentiated tumor cells contain myoglobin and rhabdomyosarcoma has previously been reported as being positive for NSE. The production of external lamina material peripherally in the tumor cell nests and around vessels in the vascular septa was demonstrated both ultrastructurally and by immunohistochemistry using antibodies against collagen IV and laminin. The cytologic appearance in smears obtained by fine-needle aspiration from a case of the pleomorphic variant showed some resemblance to that of a carcinoma. The seven tumors with an ordinary cell appearance were found to show a diploid DNA-distribution at a quantitative analysis performed on paraffin sections, while the three tumors wholly or partly of the pleomorphic type showed an additional tetraploid peak.
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PMID:Alveolar soft part sarcoma. An immunohistochemical, cytologic and electron-microscopic study and a quantitative DNA analysis. 312 65

Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells, consists of PDGF-1 and PDGF-2 polypeptide chains which are linked by disulfide bonds. Sequence analysis has revealed that: (a) the PDGF-2 chain is encoded by the c-sis protooncogene, the cellular counterpart of the simian sarcoma viral oncogene; (b) the PDGF-1 and PDGF-2 chains are related; and (c) the PDGF-1 gene has no known viral homologue. We have previously shown that the PDGF-2 gene is expressed during 12-O-tetradecanoylphorbol-13-acetate (TPA) induced monocytic differentiation of human HL-60 leukemia cells. In the present study, PDGF-1 and PDGF-2 gene expression was compared in HL-60 cells, human THP-1 monocytic leukemia cells, and human monocytes. Uninduced HL-60 cells, uninduced THP-1 cells, and resting monocytes had no detectable PDGF-1 or PDGF-2 mRNA. In contrast, both PDGF-1 and PDGF-2 transcripts were detected in HL-60 cells and monocytes induced with TPA, while only PDGF-1 mRNA was found in TPA-treated THP-1 cells. Moreover, neither of these transcripts were found during drug induced granulocytic differentiation of HL-60 cells. Cycloheximide, an inhibitor of protein synthesis: (a) failed to increase PDGF-1 and PDGF-2 mRNA levels in uninduced HL-60 cells; (b) increased PDGF-2, but not PDGF-1, mRNA in resting monocytes; and (c) increased levels of PDGF-1 and PDGF-2 mRNA in HL-60 cells and monocytes treated with TPA. This effect of cycloheximide was related in part to stabilization of both transcripts. Thus, PDGF-1 and PDGF-2 genes are differentially regulated in myeloid cells, although they share common control mechanisms at the post-transcriptional level. Differential regulation of PDGF gene expression would result in altered chain composition of the PDGF protein and possibly changes in biological activity.
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PMID:Expression of the platelet-derived growth factor 1 and 2 genes in human myeloid cell lines and monocytes. 316 51


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