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101.
Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. 总被引:58,自引:28,他引:30
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P Hu B Margolis E Y Skolnik R Lammers A Ullrich J Schlessinger 《Molecular and cellular biology》1992,12(3):981-990
One of the immediate cellular responses to stimulation by various growth factors is the activation of a phosphatidylinositol (PI) 3-kinase. We recently cloned the 85-kDa subunit of PI 3-kinase (p85) from a lambda gt11 expression library, using the tyrosine-phosphorylated carboxy terminus of the epidermal growth factor (EGF) receptor as a probe (E. Y. Skolnik, B. Margolis, M. Mohammadi, E. Lowenstein, R. Fischer, A. Drepps, A. Ullrich, and J. Schlessinger, Cell 65:83-90, 1991). In this study, we have examined the association of p85 with EGF and platelet-derived growth factor (PDGF) receptors and the tyrosine phosphorylation of p85 in 3T3 (HER14) cells in response to EGF and PDGF treatment. Treatment of cells with EGF or PDGF markedly increased the amount of p85 associated with EGF and PDGF receptors. Binding assays with glutathione S-transferase (GST) fusion proteins demonstrated that either Src homology region 2 (SH2) domain of p85 is sufficient for binding to EGF and PDGF receptors and that receptor tyrosine autophosphorylation is required for binding. Binding of a GST fusion protein expressing the N-terminal SH2 domain of p85 (GST-N-SH2) to EGF and PDGF receptors was half-maximally inhibited by 2 and 24 mM phosphotyrosine (P-Tyr), respectively, suggesting that the N-SH2 domain interacts more stably with PDGF receptors than with EGF receptors. The amount of receptor-p85 complex detected in HER14 cells treated with EGF or PDGF. Growth factor treatment also increased the amount of p85 found in anti-PDGF-treated HER14 cells, suggesting that the vast majority of p85 in the anti-P-Tyr fraction is receptor associated but not phosphorylated on tyrosine residues. Only upon transient overexpression of p85 and PDGF receptor did p85 become tyrosine phosphorylated. These are consistent with the hypothesis that p85 functions as an adaptor molecule that targets PI 3-kinase to activated growth factor receptors. 相似文献
102.
Chronic treatment of hamsters with estradiol for several months has previously been shown to decrease the specific content
of cytochrome P450 in the kidney, a target of hormonal carcinogenesis, but not in liver. The reason for this decrease in metabolic
enzyme activity is unknown and has been examined in this investigation. We now report that the decrease in specific content
of renal cytochrome P450 by 73% in response to estradiol was not affected by co-treatment with tamoxifen for 1 month. The
subcutaneous infusion of 250 μg/day estradiol for 7 days lowered renal cytochrome P450 by 71% from control values and was
therefore used for further mechanistic studies. This treatment decreased renal activities of estradiol 2- or 4-hydroxylase
by 77 to 80%, of 7-ethoxycoumarin-O-deethylase by 66% of control values, respectively, and completely eliminated aryl hydrocarbon
hydroxylase activities, whereas liver enzymes remained unaffected. After 7 days of infusion of estradiol, fluorescent products
of lipid peroxidation were more than doubled in hamster kidney but remained unchanged in liver. The possibility of enzyme
destruction by binding of estradiol 2,3-quinone to metabolizing enzymes was investigatedin vitro. In the presence of 2-hydroxyestradiol, cumene hydroperoxide, and microsomes, conditions known to favor the oxidation of
the steroid to quinone, the binding of catechol estrogen metabolite to microsomal protein increased 60 fold over control values
in the absence of cofactor. Purified rat liver cytochrome P450c also oxidized 2-hydroxyestradiol to 2,3-estradiol quinone.
The rate of oxidation was linear for the first 2–3 min, but thereafter decreased with time. Under these incubation conditions,
irreversible binding of catechol estrogen metabolite to cytochrome P450c increased for the first 2–3 min and then remained
at this plateau level. It was concluded that enzyme destruction by a reactive estrogen metabolite or by lipid peroxides may
be a major reason for the organ-specific decrease in cytochrome P450 enzymes in kidneys of estrogen-treated hamsters. 相似文献
103.
104.
Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia. 相似文献
105.
Anaerobic growth on elemental sulfur using dissimilar iron reduction by autotrophic Thiobacillus ferrooxidans 总被引:2,自引:0,他引:2
Abstract Anaerobic growth on elemental sulfur using dissimilar iron reduction by Thiobacillus ferrooxidans has been demonstrated. The ferric ion reducing activity (FIR) of the anaerobic cells was double that of the aerobic cells. Significant differences in inhibition of FIR by respiratory inhibitors were observed between aerobic and anaerobic cells. A higher amount of cytochrome was detected in anaerobic cells compared to aerobic cells. Absorption minima developed with the addition of ferric sulfate in the dithionite reduced cell suspension demonstrated that the ferric ion could accept electrons from the cytochrome system of this bacterium. The possibility of two different electron transport chains in ferric ion reduction is discussed. 相似文献
106.
Roy E. Crabtree Edward C. Cyr Renée E. Bishop Laura M Falkenstein John M. Dean 《Environmental Biology of Fishes》1992,35(4):361-370
Synopsis Leptocephali were collected in June 1981 and July 1989 over the continental shelf and slope of the Florida west coast. Tarpon larvae ranged 5.5–24.4 mm standard length (SL) and were the second most abundant leptocephalus species. Sagittae examined with compound microscopes and scanning electron microscopy had increments that were presumed to be formed daily. Increment counts made using the two microscopic techniques were not significantly different. Estimated ages ranged 2–25 days with a growth rate (± standard error) of 0.92 ± 0.04 mm d–1 The least squares linear regression equation SL = 2.78 + 0.92 (age in days) best described the relationship between estimated age and length. Adult tarpon appear to undergo a substantial spawning migration from inshore areas frequented during spring and summer to offshore spawning grounds. Spawning occurs during May, June, and July, although the spawning season may be of greater duration. 相似文献
107.
Variable expression of latent membrane protein in nasopharyngeal carcinoma can be related to methylation status of the Epstein-Barr virus BNLF-1 5''-flanking region. 总被引:7,自引:5,他引:2
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L F Hu J Minarovits S L Cao B Contreras-Salazar L Rymo K Falk G Klein I Ernberg 《Journal of virology》1991,65(3):1558-1567
Seven virus-coded proteins, the nuclear proteins EBNA-1 to EBNA-6 and the latent membrane protein (LMP), are regularly expressed in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. In nasopharyngeal carcinoma (NPC), only EBNA-1 is regularly expressed; LMP is detected in about 65% of the tumors. In Burkitt's lymphoma tumors only EBNA-1 is expressed. We have recently shown that the methylation patterns of the EBV genome varied between these cell types. In virally transformed lymphoblastoid cell lines of normal origin, the EBV DNA is completely unmethylated. In contrast, in the Burkitt's lymphoma-derived cell line Rael and in a nude mouse-passaged NPC tumor, C15, there was an extensive methylation of CpG pairs. The methylation extended into the coding regions of the two expressed genes, EBNA-1 (in both tumor types) and LMP (in C15). Two presumptive control regions were exempted from this overall methylation: the oriP that contains both an origin of DNA replication and an EBNA-1-dependent enhancer and the 5'-flanking region of the BNLF-1 open reading frame that codes for LMP. The latter was only exempted in the LMP expressing NPC. We have now investigated the relation between expression of LMP and methylation of DNA in the 5'-flanking 1 kb region of BNLF-1, coding for LMP. LMP was methylated in 3 of 12 NPC biopsies that did not express LMP but was partially or totally unmethylated in the remaining 9 that expressed the protein. The three BNLF-1 exons were highly methylated in all the tumors. The oriP region was unmethylated in all the tumors, as in the previously studied Rael cell line and nude mouse-passaged NPC. Also, the BamHI W enhancer region involved in the expression of EBNA nuclear proteins was methylated. None of the biopsies expressed EBNA-2. Our data show that the EBV genomes are highly methylated in NPC tumors. The strong reverse correlation between the methylation of the putative control region of the LMP gene and the expression of LMP suggests that methylation has a role in the regulation of this gene. 相似文献
108.
Although the acyl groups of phosphatidylserine in brain are uniquely enriched in docosahexaenoic acid (22:6n3), the mechanism for this enrichment is not well understood. When rat brain homogenates and microsomes were incubated in the presence of lysophosphatidylserine (LPS) together with [14C]22:6n3 and cofactors for activation to its acylCoA, very little radioactivity was incorporated into phosphatidylserine (PS). On the other hand, [14C]20:4n6 was more actively incorporated into PS. Addition of LPS (1-10 uM), however, resulted in a 2-5 fold enhancement of the transfer of labeled 22:6n3 and 20:4n6 to phosphatidic acid (PA). Kinetic analysis indicated the ability of LPS to lower the Km and increase the Vmax of the lysophosphatidic acid (LPA) acyltransferase reaction. Among other lysophospholipids tested, lysophosphatidylserine was most effective in enhancing PA biosynthesis. Since PA is an important intermediate for de novo biosynthesis of phospholipids, these results reveal a novel mechanism for promoting synthesis of PA enriched in polyunsaturated fatty acids in brain. 相似文献
109.
MNNG-induced killing of V79 cells has been found to be enhanced on inhibition of topoisomerase II activity by nalidixic acid and poly(ADP-ribose) polymerase synthesis by benzamide. Using these 2 inhibitors in conjunction after MNNG treatment, some overlap in the functions of these 2 enzymes was observed. Nalidixic acid and benzamide were found to suppress the yields of mutations and SCEs induced by MNNG. Benzamide was more effective in suppressing the mutation yield whereas nalidixic acid was more effective in suppressing SCEs. A model based on the relative requirement of topoisomerase and poly(ADP-ribose) for the repair of different types of damage has been proposed to explain the results. 相似文献
110.