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

Previous studies of premature chain termination mutants and in frame deletion mutants of the p21 ras transforming protein encoded by the transforming gene of Harvey murine sarcoma virus (Ha-MuSV) have suggested that the C terminus is required for cellular transformation, lipid binding, and membrane localization. We have now further characterized the post-translational processing of these mutants and have also studied two C-terminal v-rasH point mutants: one encodes serine in place of cysteine-186, the other threonine for valine-187. The Thr-187 mutant was transformation-competent, and its p21 protein was processed normally, as was the p21 encoded by a transformation-competent deletion mutant from which amino acids 166-175 had been deleted. The Ser-186 mutant was defective for transformation. The p21s encoded by the Ser-186 mutant and by the previously described transformation-defective mutants did not undergo the posttranslational processing common to biologically active ras proteins: their electrophoretic migration rate did not change, they remained in the cytosol, and they failed to bind lipid. Since the cell-encoded ras proteins also contain this cysteine, we conclude that this amino acid residue is required for all ras proteins.
 ...
PMID:Harvey murine sarcoma virus p21 ras protein: biological and biochemical significance of the cysteine nearest the carboxy terminus. 609 32

Enhancement of endogenous xenotropic virus expression has been found upon treatment with tetrapeptides of a high-passage clone of Balb/c (K-Balb) mouse cells transformed with Kirsten sarcoma virus. Tuftsin (Thr-Lys-Pro-Arg) and kentsin (Thr-Pro-Arg-Lys) increased the expression of virus that was infectious for rat, but not mouse, cells in a concentration-dependent fashion. The enhancement of virus expression by the tetrapeptides was proportional to the spontaneous release of virus. The infectivity of the enhanced virus was neutralized by goat anti-RLV gp70 serum. Actinomycin D inhibited the induction of virus, suggesting that enhanced expression required de novo RNA synthesis. The effects observed using K-Balb cells offer an opportunity to study the many biological effects of these peptides in a fibroblast culture system.
 ...
PMID:Increased expression of endogenous xenotropic murine retrovirus by treatment with the tetrapeptides, tuftsin and kentsin. 616 63

The purified p21src protein of Harvey sarcoma virus shows a guanine nucleotide-binding activity and, in addition, at elevated temperature an autophosphorylating activity at a threonine residue using as phosphoryl donor GTP or dGTP but not ATP or dATP. These biochemical activities are unique among those associated with transforming proteins of RNA-containing or DNA-containing tumour viruses.
 ...
PMID:Guanine nucleotide-binding and autophosphorylating activities associated with the p21src protein of Harvey murine sarcoma virus. 625 10

The transforming protein coded for by the onc gene (v-rasHa) of Harvey murine sarcoma virus (Ha-MuSV) is the 21,000-dalton protein (p21) which is the immediate agent responsible for the virus-induced malignant transformation of normal cells. The p21 proteins of Ha-MuSV and the closely related Kirsten murine sarcoma virus are heavily phosphorylated in vivo. In the partially purified Ha-MuSV p21, the protein shows a guanine nucleotide-binding activity and, in addition, a very unique autophosphorylating activity at a threonine residue using as phosphoryl donor GTP but not ATP. In the present study, we compared the tryptic peptide maps of the Ha-MuSV p21 phosphorylated in vivo and in vitro. The results show that the major phosphorylation site is identical. Since the GTP-specific phosphorylation is very unique and distinct from all other known protein kinases, the present observation suggests that the in vitro enzymatic activity is responsible for the p21 phosphorylation in vivo. We have analyzed the amino acid sequence surrounding the major phosphorylation site of the Ha-MuSV p21 by automated Edman degradations of the tryptic phosphopeptides. Threonine residue 59 from the initiator methionine residue 1 of the p21 protein is the phosphorylated amino acid residue, and the surrounding amino acid sequence is NH2...-Thr-Cys-Leu-Leu-Asp-Ile-Leu-Asp-Thr-Thr(P)-Gly-Gln-Glu-Glu-Tyr-...COOH. The p21 proteins of both the Ha-MuSV and the closely related Kirsten murine sarcoma virus share the same phosphopeptide. The amino acid sequence of the phosphorylation site is distinct from all other known protein kinases.
 ...
PMID:Characterization of the phosphorylation sites and the surrounding amino acid sequences of the p21 transforming proteins coded for by the Harvey and Kirsten strains of murine sarcoma viruses. 628 98

The transforming proteins (p21) of Harvey and Kirsten sarcoma viruses threonine kinase activity, which phosphorylates threonine 59 of the p21 proteins themselves. A tridecapeptide: Arg-Arg-Leu56-Asp-Thr-Thr59-Gly-Gln-Glu-Tyr-Ser-Ala66 containing residues 56-66 of p21 is phosphorylated solely on tyrosine by the epidermal growth factor (EGF)-stimulated tyrosine kinase of A431 cell membranes. Km-Values of 240 and 80 microM and Vmax values of 1.7 and 0.1 nmol.min-1.mg-1 were obtained in the presence and absence of EGF, respectively.
 ...
PMID:A synthetic peptide containing the autophosphorylation site of the transforming protein of Harvey sarcoma virus is phosphorylated by the EGF-stimulated tyrosine kinase. 631 15

In this paper the synthesis of the following elongated tuftsin analogs: Thr-Lys-Pro-Lys-Thr-Lys-Pro-Lys (I), Thr-Lys-Pro-Lys-Thr-Lys-Pro-Arg (II) and Ala-Lys-Thr-Lys-Pro-Arg-Glu-Gln (III) by the classical method is described. The compound II markedly inhibited the growth of murine sarcoma viruses (MSV).
 ...
PMID:Synthesis and biological investigations of new tuftsin analogs with elongated peptide chain. 631 64

The exposure of a high-passage clone of Kirsten sarcoma virus transformed Balb/c (K-Balb) mouse cells to tuftsin (Thr-Lys-Pro-Arg) enhanced the expression of endogenous xenotropic retrovirus. The tetrapeptide increased the expression of virus that was infectious for rat, but not mouse, cells in a concentration-dependent fashion (0.001-1000 micrograms/ml). Increased virus expression could be achieved during short-term incubations (3-4 hr), with maximum enhancement occurring over longer time periods (16-18 hr). The enhancement of virus expression by tuftsin was proportional to the spontaneous release of virus. The infectivity of the enhanced virus was neutralized by goat anti-RLV gp 70 serum. Actinomycin D inhibited the induction of virus, suggesting that enhanced expression required de novo RNA synthesis. Tuftsin stimulated DNA, RNA, and protein synthesis in K-Balb cells during 16-hr incubations. Increased cellular proliferation was also seen at various time periods. The effects observed using K-Balb cells offer an opportunity to study the modulation of gene expression by tuftsin in a fibroblast culture system.
 ...
PMID:Enhancement of endogenous xenotropic murine retrovirus expression by tuftsin. 632 38

Retroviruses carry cell-derived oncogenes (v-onc) that have the potential to transform cells in culture and induce tumours in vivo. One of the few carcinoma-inducing viruses is the acutely transforming retrovirus MH2, which carries the putative oncogene v-mil and the known oncogene v-myc. Recently, a high degree of homology was discovered between v-mil and v-raf, the transforming gene of the murine retrovirus 3611 murine sarcoma virus (MSV), whereas homology to v-src is low. Both viruses express their oncogenes as the gag-fusion polyproteins p100gag-mil and p75gag-raf (of respective relative molecular mass (Mr) 100,000 and 75,000), while the myc oncogene of MH2 is expressed by means of a subgenomic messenger RNA. We have recently demonstrated that p100gag-mil is not a nuclear protein. Here we report that purified p100gag-mil and p75gag-raf exhibit protein kinase activities in vitro which, in contrast to the src-related p130gag-fps of Fujinami sarcoma virus (FSV) and all other characterized oncogene-encoded protein kinases, phosphorylate serine and threonine but not tyrosine. Both types of protein kinases phosphorylate lipids in vitro.
 ...
PMID:Serine- and threonine-specific protein kinase activities of purified gag-mil and gag-raf proteins. 643 34

The 21,000-dalton protein (p21) encoded by the ras oncogene of Harvey murine sarcoma virus (v-Ha-ras) becomes phosphorylated (pp21) in vivo and in vitro on threonine residue 59. p21 molecules encoded by cellular ras genes (c-Ha-ras-1) contain an alanine at position 59, and thus these p21 molecules are not phosphorylated. In this investigation, recombinant ras genes have been constructed between the 5' p21 coding region of normal (EC) or oncogenically activated (EJ) human c-Ha-ras-1 and the 3' p21 coding region of v-Ha-ras to generate p21 molecules containing a threonine phosphoacceptor site at position 59 and a glycine (EC/v-Ha) or valine (EJ/v-Ha) at residue 12. In transformed NIH 3T3 mouse fibroblast cells labeled with [35S]methionine, the ratio of pp21 to p21 was strikingly modulated by the amino acid at residue 12. v-Ha-ras p21 has an arginine at position 12, and 24% of total p21 was in the phosphorylated form. A glycine at residue 12 decreased the amount of pp21 to 14% of total p21, and a valine at residue 12 dramatically increased this value to 50%. In vitro, the valine form of p21 had 2.4- and 2.7-fold greater autophosphorylating activity than the glycine and arginine forms of p21, respectively, using [gamma-32P]GTP as phosphate donor, but the three p21 species had similar Km values for GTP (0.20-0.27 microM). These results indicate that a biochemical activity of p21 distinguishes between previously observed biological differences of normal and activated human ras genes.
 ...
PMID:Autophosphorylation of v-Ha-ras p21 is modulated by amino acid residue 12. 660 66

The temporal relationship between butyrate-induced cellular flattening of murine sarcoma virus-transformed rat cells (MSV-NRK) and alterations in certain surface-associated biochemical markers of transformation, e.g., surface glycopeptides, glycolipids, fibronectin, hexose uptake, and cell-substrate adhesion was examined. The induction of elevated levels of the ganglioside GM3 and of a GDla-like ganglioside were observed to precede or to parallel cellular flattening. Likewise, enhanced incorporation of radioisotopically labeled fucose into a novel fucose-containing component, i.e., glucopyranosyl (1 leads to 3) fucopyranosyl-threonine, was also observed to occur at an early stage of cellular flattening. In contrast, a shift in the molecular weight distribution of trypsin-sensitive, surface fucopeptides was observed to occur at a late stage of cellular flattening. Moreover, surface fibronectin was not detectable in the butyrate-flattened MSV-NRK cells despite the fact that the cells manifested significantly enhanced cell-substrate adhesion. Thus, butyrate appears to be a useful tool for understanding the sequential changes associated with expression of the transformed phenotype of MSV-NRK cells.
 ...
PMID:Effects of sodium butyrate on the membrane glycoconjugates of murine sarcoma virus-transformed rat cells. 738 Aug 82


<< Previous 1 2 3 4 5 6 Next >>