Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymerase chain reaction techniques and medium stringency library screening were used to isolate a rat cDNA ("H218") which encodes a novel guanine nucleotide-binding protein coupled receptor homolog ("pH218"). Northern analysis revealed that brain H218 mRNA is preferentially expressed during embryogenesis. In addition, H218 mRNA is expressed in all developing tissues and rodent cell lines examined with highest levels detected in primitive, transformed cells. H218 mRNA expression in cell lines is rapidly increased by a tumor promoter and rapidly decreased by a differentiation-inducing growth factor. Finally, all of the sequence motifs characteristic of Src homology 2 domains are present in pH218 but in a unique arrangement. We conclude that pH218 may function as a growth factor receptor.
Mol Cell Neurosci 1994 Jun
PMID:Cloning and characterization of a putative G-protein coupled receptor potentially involved in development. 808 18

Hotspots are a standard feature of mutational spectra induced by mutagens in a variety of marker genes. While it is generally believed that sequence context exerts an important influence on hotspot location, direct experimental evidence is quite limited. We have studied ultraviolet mutagenesis in a suppressor tRNA marker gene (supF) carried in a mammalian shuttle vector and replicated in Xeroderma pigmentosum cells in culture. We have now constructed a small family of functional variant suppressor tRNA marker gene which differ from one another by one or two nucleotide changes. UV mutational spectra were generated for each variant gene. We found that the change of a dipyrimidine from 5' TC to 5' CC eliminated a strong mutational hotspot. In addition a single base change in the supF gene was accompanied by the appearance of a new hotspot eight bases away. Finally, another single base change suppressed a major hotspot 48 bases away. Polymerase stop assays on the UV modified marker genes were used to measure the frequency and distribution of photoproducts. The differences in hotspot patterns could not be explained by differences in modification patterns. These results indicate that a change in sequence context can directly influence the probability of mutagenesis at specific sites.
J Mol Biol 1994 Feb 18
PMID:Proximal and distal effects of sequence context on ultraviolet mutational hotspots in a shuttle vector replicated in xeroderma cells. 810 35

Polymerase chain reaction has for the first time been shown to be applicable to indication of Leptospira interrogans in the organs of infected animals with acute or chronic leptospirosis (on the model of golden syrian hamsters). Polymerase chain reaction is superior to microscopic and bacteriological analyses in identification of leptospirae in organ suspensions. The sensitivity of the technique is 1-10 cells per sample in studies of kidney or brain suspensions or 100-1000 cells in studies of liver suspensions.
Mol Gen Mikrobiol Virusol
PMID:[A polymerase chain reaction method for studying host persistence of pathogenic leptospira]. 813 45

p53 genes were analyzed for mutations and expression in a series of 24 tumors or hyperplastic lesions of the urinary bladder induced in F344 rats by carcinogen treatment. Of these, 18 were analyzed as short-term urothelial cultures. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing were used to detect alterations in p53 genes or cDNAs, and the relative amounts of p53 protein per cell were estimated by immunohistochemical staining. Missense substitutions were found in the exon 5-9 region of two of five cell cultures analyzed from lesions induced by the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. One of these was a papillary nodular hyperplasia, indicating that p53 mutations can be present in low- as well as high-stage/grade bladder lesions. p53 mutations were not found in the exon 5-9 region in cells of any of eight bladder lesions induced by N-[4-(5-nitro-2-furyl)-2- thiazoly]formamide (FANFT), including five transitional cell carcinomas (TCCs), or either of two TCCs induced by N-methylnitrosourea. Two of nine TCCs induced by the N-glucuronide of N-hydroxy-2-aminofluorene were found to have p53 mutations. One of these was evidently altered by three genetic events: a missense substitution in exon 8, a nonsense mutation in exon 6, and silencing of the "nonsense" allele (i.e., only the p53 missense mutation was detected). Immunohistochemical analysis with monoclonal antibody PAb240 (which preferentially binds to mutant p53 protein) detected p53 antigen only in those samples in which missense p53 mutations were found. With monoclonal antibody PAb421 (which detects mutant and wild-type p53), p53 antigen was also detected in cells from F542, a bladder tumor induced by FANFT in which no p53 mutations were found. Northern blot hybridization analysis showed that p53 transcripts were elevated twofold to threefold in several cases, including F542, suggesting that constitutive overexpression of wild-type p53 may occur in some bladder neoplasias. These data support the view that p53 may be involved in multiple rate-limiting steps in neoplastic transformation and may be a continuing target during bladder carcinogenesis. The data also contribute to evidence that certain chemical carcinogens may directly alter p53 genes during tumorigenesis.
Mol Carcinog 1994 Feb
PMID:Mutation and altered expression of p53 genes in experimental rat bladder tumor cells. 814 14

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a very potent mutagen that is carcinogenic in rodents and nonhuman primates. IQ-induced CDF1 mouse lung and liver tumors were examined for activated Ki-ras and Ha-ras genes, respectively. Polymerase chain reaction (PCR)-amplified target DNAs were analyzed for mutations of codons 12, 13, and 61 by single-strand conformation polymorphism (SSCP) and direct sequencing methods. All mutations were localized to codon 61 of the ras genes. Forty-nine of 54 lung tumors induced by IQ possessed activating Ki-ras mutations, as did 20 of 26 lung tumors from the vehicle-treated animals; 80% and 75% of these mutations, respectively, were A-->T transversions of the second nucleotide redundant. One lung adenoma from the IQ-treated group contained a tandem duplication of the sequence corresponding to codons 50-57 of the Ki-ras gene (unpublished observations). In addition, seven of 34 IQ-induced liver tumors harbored activating Ha-ras mutations: five were C-->A (G-->T) transversions at the first nucleotide, and two were A-->T transversions at the second nucleotide of codon 61. None of the 15 liver tumors collected from the vehicle-treated mice possessed Ha-ras mutations in codon 12, 13, or 61. These data indicate that IQ induces Ha-ras gene activation in CDF1 mouse liver tumors. The mechanisms of lung tumor induction by IQ, however, is obscured by the high frequency of Ki-ras A-->T mutations observed in both the IQ-induced and spontaneous lung tumors. The different ras mutational spectra in lung and liver tumors may suggest either that two different pathways of IQ metabolism exist in these organs or that IQ contributes to CDF1 lung tumorigenesis by a mechanism other than its direct interaction with the Ki-ras gene.
Mol Carcinog 1993
PMID:ras mutations in 2-amino-3-methylimidazo-[4,5-f]quinoline-induced tumors in the CDF1 mouse. 821 39

The Mouse Mammary Tumor Virus (MMTV) long terminal repeat contains an open reading frame (orf) of 960 nucleotides encoding a 36 kDa polypeptide with a putative transmembrane domain and five N-glycosylation sites in the N-terminal part of the protein. Transgenic mice bearing either the complete or the 3' terminal half of the orf sequence of MMTV-GR under the control of the SV40 promoter were raised. As shown previously by FACS analysis transgenic mice which express the complete orf gene have a significant deletion of V beta 14 expressing T cells at 6 weeks of age. Here we show that no clonal deletion of V beta 14 bearing T cells takes place in transgenic mice that contain orf sequences from the fifth ATG to the termination codon. The pattern of tissues expressing the truncated transgene was studied by the Polymerase Chain Reaction (PCR) and was very similar to the one obtained in the V beta 14 deleting animals. These data suggest that the amino-terminal portion of the ORF protein (pORF) is required for a superantigen function, while our previous data indicated that determinants from the carboxy-terminus play an important role for TCR V beta specificity.
Mol Immunol 1993 Nov
PMID:The 3' half of the mouse mammary tumor virus orf gene is not sufficient for its superantigen function in transgenic mice. 823 25

The Palo Alto strain of Plasmodium falciparum is highly virulent for the Saimiri sciureus monkey. We have observed that these parasites do not express the Ring-infected erythrocyte surface antigene (RESA) gene. Immunoblots indicated that the Pf155/RESA protein was absent. The RESA mRNA could not be detected. Polymerase chain reaction and Southern blot analysis demonstrated that this lack of expression is due to gene rearrangements. The majority of the Palo Alto parasites have a deletion of the entire RESA gene, whereas in a minor fraction the RESA sequences remain detectable, but the 5' miniexon 1 is inverted. These data show that the RESA protein is dispensable for in vivo parasite growth, at least in Saimiri monkeys.
Mol Biochem Parasitol 1993 Aug
PMID:The virulent Saimiri-adapted Palo Alto strain of Plasmodium falciparum does not express the ring-infected erythrocyte surface antigen. 823 15

To understand the regulation of A2a adenosine receptor (A2a-R) response, we examined the molecular mechanisms underlying the desensitization of A2a response in rat pheochromocytoma PC12 cells, which possess an A2a-R identical with the A2a receptor we recently cloned from rat brain. Prolonged exposure of PC12 cells to adenosine agonists significantly inhibited the response of the cells to subsequent stimulation with an A2a-selective adenosine agonist (CGS21680). No significant change in the number of binding sites and affinity for CGS21680 was observed in desensitized cells, nor did we find any significant change in the transcript level of A2a-R in cells pretreated with adenosine agonists. However, the basal adenylyl cyclase activity and the cyclase activities stimulated by adenosine agonists, by GTP gamma S, and by forskolin were reduced in desensitized cells. Prolonged exposure of PC12 cells to dibutyryl-cAMP did not significantly change either the basal or the adenosine agonist-evoked adenylyl cyclase activity. Therefore, elevation of cellular cAMP content is by itself not sufficient to produce the observed reductions of adenylyl cyclase activity with A2a desensitization. Inhibition of adenylyl cyclase activity in desensitized cells occurred after short-term (30 min) incubation with CGS21680 and could be blocked by the adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine. Gs alpha protein levels did not significantly change after a 30-min exposure to CGS21680. In contrast, long-term exposure (12-20 hr) of PC12 cells to adenosine agonists resulted in a slight further reduction of adenylyl cyclase activity and a consistent decline in the Gs alpha protein level. In addition, long-term incubation with adenosine agonists or with forskolin-enhanced phosphodiesterase (PDE) activity in the cytosolic and membrane fractions by 57 +/- 9% and 53 +/- 18%, respectively. Hydrolysis of cAMP was significantly faster in agonist-desensitized cells than in control cells. PDE might therefore play an important role in desensitization of the A2a response in PC12 cells. Polymerase chain reaction-based analysis of the mRNA for A2a-R and A2b-R indicated that both A2a-R and A2b-R were present in PC12 cells; the A2b response was also diminished in A2a-desensitized cells. Our data suggest that inhibition of adenylyl cyclase after short-term agonist treatment, down-regulation of Gs alpha protein level after long-term agonist treatment, and activation of PDE after long-term agonist treatment account for desensitization of the A2a-mediated response in PC12 cells.
Mol Pharmacol 1993 Nov
PMID:Multiple mechanisms for desensitization of A2a adenosine receptor-mediated cAMP elevation in rat pheochromocytoma PC12 cells. 824 18

There is significant evidence that the ras oncogene plays a role in experimental mammary carcinogenesis; the evidence in human breast cancer, however, is more limited. We induced the expression of transformation phenotypes in the human breast epithelial cell line MCF-10F with the chemical carcinogens 7,12-dimethylbenz[a]anthracene, N-methyl-N-nitrosourea, N-methyl-N-nitro-N'-nitrosoguanidine, and benzo[a]pyrene. This work was designed to clarify whether chemically induced neoplastic transformation correlates with alterations in the ras gene. MCF-10F cells have two c-Ha-ras alleles, identified by 1.0-kb and 1.2-kb restriction fragments. Treatment with carcinogens resulted in the loss of one of the alleles (1.0 kb). Polymerase chain reaction-amplified DNA from all carcinogen-treated cells was analyzed for point mutations in c-Ha-ras at codons 12 and 61. All of the carcinogens induced a mutation of the remaining allele at the first position of codon 12 (GGC-->AGC). Another frequent mutation occurred at the first position of codon 61 (CAG-->GAG). The changes in c-Ha-ras were associated with the emergence of colony formation in agar-methocel, but no specific changes in this gene correlated with the emergence of invasiveness or tumorigenesis, indicating that other genes may be involved in the process.
Mol Carcinog 1994 Jan
PMID:Allele loss and point mutation in codons 12 and 61 of the c-Ha-ras oncogene in carcinogen-transformed human breast epithelial cells. 829 85

Previous analyses have demonstrated that, among the echinoderms, the sea star (class: Asteroidea) mitochondrial genome contains a large inversion in comparison to the mitochondrial DNA of sea urchins (class: Echinoidea). Polymerase chain reaction amplification, DNA cloning, and sequencing have been used to examine the relationships of the brittle stars (class: Ophiuroidea) and sea cucumbers (class: Holothuroidea) to the sea stars and sea urchins. The DNA sequence of the regions spanning potential inversion junctions in both brittle stars and sea cucumbers has been determined. This study has also revealed a highly modified tRNA cluster in the ophiuroid mitochondrial genome. Our data indicate mitochondrial gene arrangement patterns that group the sea cucumbers with sea urchins and sea stars with brittle stars. This use of molecular characters clarifies the relationships among these classes.
J Mol Evol 1993 Jun
PMID:The phylogeny of echinoderm classes based on mitochondrial gene arrangements. 835 Mar 49


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