Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Sulphated cholecystokinin octapeptide (CCK8S, 0.03-1.00 microM), pentapeptide (CCK5) and tetrapeptide (CCK4) elicited concentration dependent depolarizations of neonate rat ventral roots in vitro. 2. CCK5 was equipotent with CCK8S although CCK4 was weaker (equipotent molar ratio 17.5). 3. CCK8S-induced depolarizations were depressed by tetrodotoxin (0.1 microM), Mg2+ ions (0.75 mM) and the NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5, 10 microM). These results suggest that CCK8S-induced depolarizations were predominantly mediated through the release of an excitatory amino acid from interneuronal sites. 4. The selective CCKA and CCKB receptor antagonists, L-364,718 and L-365,260 both depressed CCK8S-induced depolarizations. CCK8S dose ratios in the presence of 1 microM L-364,718 or L-365,260 were 4.5 and 11.2 respectively, suggesting the response was mediated predominantly through stimulation of CCKB receptors. 5. These results suggest that the neonate rat hemicord preparation is a suitable tissue for functional CCK receptor assays.
Gen Pharmacol 1993 Jan
PMID:Cholecystokinin-induced ventral root depolarization of neonate rat hemicord in vitro. 809 38

The nucleotide sequence of the helper component protease (HC-Pro) genes of three zucchini yellow mosaic virus (ZYMV) strains has been compared with that of a helper-deficient strain of ZYMV-HC. The comparisons revealed three unique deduced amino acid differences. Two of these mutations were located in regions which are conserved in other potyviruses. The role of these mutations in aphid transmissibility was examined by exchanging DNA fragments of part of the deficient HC-Pro gene with the respective section within the gene of the infectious full-length clone of the aphid-transmissible ZYMV. The first exchange included two of the three mutations, the first coding for a change from Asp to Gly (in a non-conserved region) and the second coding for a change from Arg to Ile [within the Phe-Arg-Asp-Lys (FRNK) conserved box]. This exchange resulted in a reduced transmission (20.6% for the mutated virus compared with 57.4% in the normal ZYMV when acquired from plants and 37.2% compared with 83.1%, respectively, when acquired from membranes). The second exchange incorporated a single mutation [conferring a change from Thr to Ala within the Pro-Thr-Lys (PTK) conserved box]. This single mutation resulted in almost total loss of HC activity in aphid transmission both from plants and from membranes. The Lys residue in the conserved Lys-Ile-Thr-Cys (KITC) box, which is related to loss of HC activity in potato virus Y, tobacco vein mottling virus and in the Michigan strain of ZYMV, is unchanged in the helper-deficient ZYMV. It is therefore proposed that more than one site in HC-Pro may be functionally related to aphid transmissibility. The possible reasons for the role of these mutations in helper activity in aphid transmission of ZYMV are discussed.
J Gen Virol 1994 Jun
PMID:Mutations in the helper component protease gene of zucchini yellow mosaic virus affect its ability to mediate aphid transmissibility. 820 4

The gene products of herpes simplex virus type 1 UL46 and UL47 enhance the efficiency of alpha TIF (VP16)-mediated alpha gene expression through an unknown mechanism of action. To further characterize the function of the UL46- and UL47-encoded proteins during virus infection, a series of isogenic herpes simplex virus type 1 strain F-derived UL46 and UL47 single-deletion mutants and a UL46/47 double-deletion mutant were constructed and compared with the wild type. Analysis of purified virions obtained from the UL46 deletion mutant showed for the first time that UL46 encoded the viron tegument phosphoproteins VP11 and VP12 (VP11/12). Similar analyses of the UL47 deletion mutants confirmed an earlier report by McLean et al. that UL47 also encoded two virion tegument phosphoproteins, VP13 and VP14 (VP13/14) (G. McLean, F. Rixon, N. Langeland, L. Haarr, and H. Marsden, J. Gen. Virol. 71:2953-2960, 1990). Kinetic analysis demonstrated a delay of approximately 2 h in the appearance of thymidine kinase (TK) activity in all of the UL46 and UL47 single-deletion mutants. In the UL46/47 double-deletion mutant, the delay in TK activity increased twofold, suggesting that the proteins encoded by UL46 and UL47 may act at the same level. Since the delay in TK expression occurred within the first 4 h of infection, the actions of VP11/12 and VP13/14 resulted from their virion association and not from their de novo synthesis as late (beta gamma and gamma) genes. Densitometric analysis of purified virions showed that the levels of VP11/12 and VP13/14 in the virion tegument were near the molar ratios of alpha TIF. On the basis of these observations, we predict that the abilities of UL46 and UL47 to enhance alpha TIF-mediated transcription could result from a stoichiometric association of VP11/12 and VP13/14 with alpha TIF within the infecting virion.
 ...
PMID:Herpes simplex virus type 1 UL46 and UL47 deletion mutants lack VP11 and VP12 or VP13 and VP14, respectively, and exhibit altered viral thymidine kinase expression. 838 6

The expression of both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), and of their receptors (EGFR and PDGFR) was immunohistochemically examined in 37 cases of osteosarcoma. Furthermore, immunostaining for p53 protein and Ki-67 antigen by MIB-1 was carried out and compared with the above results. EGFR (81%) expressed more often than EGF (51%) and the expression of EGF and EGFR, and PDGF and PDGFR were recognized in 49% and 38%, respectively. In eleven cases (30%), the expression of both growth factors and their receptors was combined. Anaplastic osteosarcoma showed higher MIB-1 index than osteoblastic and fibroblastic subtypes (P < 0.05). High grade osteosarcomas (G3 and G4) revealed higher MIB-1 index compared with low grade tumors (G1 and G2). PDGF positive tumors (MIB-1 index: 20.0) showed significantly higher proliferation compared with PDGF negative tumors (MIB-1 index: 6.5) (P < 0.01). Five out of 37 cases (13.5%) showed positive immunoreaction for p53. There was no correlation of p53 status with MIB-1 index and the expression of growth factors or their receptors. Our results suggest that PDGF expression may be an important mediator of cell proliferation control, via an autocrine mechanism, in human osteosarcoma.
Gen Diagn Pathol 1995 Oct
PMID:Expression of growth factors and their receptors in human osteosarcomas. Immunohistochemical detection of epidermal growth factor, platelet-derived growth factor and their receptors: its correlation with proliferating activities and p53 expression. 854

The c-met proto-oncogene product is the tyrosine kinase receptor for hepatocyte growth factor. To gain insights into its functions in the liver, we carried out a study of the expression and tyrosine phosphorylation status of the Met protein during hepatic regeneration and in human hepatocellular carcinomas. Following partial hepatectomy of rats, decreased expression of the proreceptor p170MET and reduced levels of tyrosine phosphorylation were seen within 12 h. These changes were still evident 7 days later. By contrast, there was no significant alteration of the Met beta subunit. The analysis of samples from 18 patients with hepatocellular carcinoma revealed that the expression of p160MET proreceptor was increased in non-cancerous areas, while that of the p145 beta MET proreceptor was significantly greater in the tumor tissue than in the non-tumor areas (p < 0.05). These findings suggest that processing of the Met proreceptor is closely associated with regeneration and carcinogenesis of the liver.
Gen Diagn Pathol 1996 Mar
PMID:Analysis of the hepatocyte growth factor receptor in regeneration and oncogenesis of the liver. 870 80

Primary cerebral lymphomas (PCL's) are rare tumors which, however, occur with increasing frequency. The present study investigated 55 PCL's of B-cell type, 36 in immunocompetent and 19 in AIDS-patients and 6 cases of intravascular lymphomatosis. In immunocompetent patients, proliferative indices as evaluated by PC10 and MIB1 reflected the histologic grade. Low grade tumors had a mean PCNA and MIB-1 count of 19 and 18.8 (SD 14.7 and 13.2), respectively, and high grade neoplasias showed counts of 56.7 and 47.1 (SD 19 and 17.4), respectively. No correlation of both indices with patient survival was found. 21 cases (58.3%) displayed p53-positivity of varying degree and 19 cases (52.7%) harbored bcl-2 positive neoplastic cells. Immunocompetent cases were always negative for Epstein-Barr virus RNA and lmp-1-protein. In AIDS-cases, 13 cases (68.4%) showed up lmp-1 positivity and 15 cases (78.9%) had EBER-RNA. bcl-2 positive cells were detected in 5 cases (26.3%) and all cases were p53-negative. These results are in keeping with a role of EBV in the pathogenesis of primary cerebral lymphomas in AIDS-, but not in immunocompetent patients. None of the cases with intravascular lymphomatosis showed an expression of bcl-2 or p53 oncoproteins or lmp-1 and none had EBER-RNA.
Gen Diagn Pathol 1996 Mar
PMID:Primary non-Hodgkin lymphomas of the CNS-proliferation, oncoproteins and Epstein-Barr-virus. 870 88

We investigated unusual structures produced in BHK-21 cells infected with rabies virus (HEP-Flury strain). Sellers' staining of the cells revealed, in addition to Negri body-like structures (inclusion bodies), production of a fuchsin-stained cytoplasmic structure (FCPS) which encircled the nucleus. The frequency of the FCPS-forming cells increased as replication progressed. The FCPS was different from the inclusion body because the former contained the viral glycoprotein (G) and matrix protein (M2) antigens, while the latter contained nucleocapsid antigens. In the early phase of infection, we observed accumulation of viral envelope antigens in a cytoplasmic structure that was considered to be expanded rough endoplasmic reticulum (rER) because of its concomitant increase in BiP content. Time-course studies suggested that the envelope antigen-containing structure, which was not stained with basic fuchsin, translocated to the perinuclear region to form the FCPS. FCPS formation was dependent on incubation temperature and was decreased at 30 degrees C, while the development of virus-induced cytopathic effect (CPE) was delayed. When the incubation temperature was shifted up to 37 degrees C, FCPS formation was induced again and progression of CPE was accelerated in approximate proportion to the increasing number of FCPS-positive cells. From these studies, we conclude that viral G proteins gradually accumulate in the rER with M2 protein and the expanded rER converts eventually into the FCPS, which may be closely related to accelerated host cell death.
J Gen Virol 1996 Sep
PMID:Studies on unusual cytoplasmic structures which contain rabies virus envelope proteins. 881 Oct 13

Efficient transcription elongation by RNA polymerase I (Pol I) requires a specific Pol I-associated factor, termed TIF-IC. Here we show that TFIIS, a factor that has previously been shown to promote read-through past many types of blocks to elongation by RNA polymerase II, also enhances Pol I-directed transcription elongation. In a reconstituted transcription system containing purified proteins, TFIIS stimulates Pol I transcription by increasing the overall rate of RNA chain elongation. As with Pol II, ternary Pol I complexes cleave the 3' end of the nascent transcripts in response to TFIIS. The truncated RNAs remain bound to the template, are subject to pyrophosphorolysis, and can be chased into longer transcripts. Moreover, we show by immunoprecipitation and specific affinity chromatography that TFIIS physically interacts with Pol I. The results suggest that nascent transcript cleavage by TFIIS or a TFIIS-related factor may be a general mechanism by which both Pol I and Pol II can bypass transcriptional impediments.
Mol Gen Genet 1996 Sep 25
PMID:TFIIS binds to mouse RNA polymerase I and stimulates transcript elongation and hydrolytic cleavage of nascent rRNA. 887 42

Epstein-Barr virus (EBV) initiates infection of normal B lymphocytes by binding to CD21, a complement receptor. Since EBV, unlike most viruses, preferentially infects resting (non-activated) cells, the present studies were undertaken to evaluate the hypothesis that intracellular signalling pathway(s) triggered by EBV binding to CD21 activate the expression of certain cellular genes, as well as the initially expressed viral genes, and thus enable EBV to infect resting B cells. Experiments with nontransforming EBV, recombinant virus ligand and anti-CD2 1 MAbs show that EBV binding to CD21 on resting B cells increases CD23 mRNA levels independently of viral gene expression. A panel of five protein kinase C (PKC) and tyrosine kinase (PTK) inhibitors, all with different modes of action, exhibited a distinctive pattern of effects on the EBV induced induction of CD23 expression, ranging from nearly complete inhibition to no influence. The results suggest that distinct PKC isoforms and PTKs are involved in the signalling pathway(s) triggered by EBV binding to CD21. Significantly, the five inhibitors showed the same pattern of effects on the earliest stages of infection (EBNA-2 transcription) and B cell transformation (mitogenesis and colony formation). The identical pattern of effects of these PKC and PTK inhibitors with diverse mechanisms of action on the EBV induced increase in both CD23 and EBNA-2 mRNA levels strongly suggests that their transcription is mediated by an intracellular signalling pathway which shares, at least in part, common members.
J Gen Virol 1996 Dec
PMID:Epstein-Barr virus binding to CD21, the virus receptor, activates resting B cells via an intracellular pathway that is linked to B cell infection. 900 Jan

This study investigated the pathways to many monoamines and their metabolites in the central nervous system of the frog Rana nigromaculata and the toad Bufo bufo japonicus during embryonic development and metamorphosis. Metabolites were analyzed by three-dimensional HPLC. The two species provided evidence of similar pathways, with slightly different timetables for the development of their monoamine systems. During embryonic development, the main metabolic pathways in entire embryos were tyrosine (TYR)-->[3,4-dihydroxyphenylalanine in Bufo]-->3-hydroxytyramine-->norepinephrine or epinine (EPIN)-->epinephrine, TYR-->tyramine--> (octopamine in Rana) and TYR-->3-O-methyldopa for catecholamines, and tryptophan-->kynurenine and 5-hydroxytryptamine (5-HT)-->[5-hydroxyindoleacetic acid and N-methyl-5-hydroxytryptamine (N-MET) in Bufo]. The monoamine system in the brain was similar during metamorphosis to that during embryogenesis with a few exceptions. The most striking change was the development of the bufotenine (5-hydroxy-N, N-dimethyltryptamine) pathway from 5-HT via N-MET. EPIN and norepinephrine in Rana and octopamine in both species disappeared during metamorphosis. These results are discussed in relation to the roles of the various pathways in development.
Gen Comp Endocrinol 1997 Jun
PMID:The metabolism of biogenic monoamines during embryogenesis and metamorphosis in two anuran species. 920 70


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