排序方式: 共有24条查询结果,搜索用时 15 毫秒
1.
Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins 总被引:9,自引:0,他引:9
Decay-accelerating factor (DAF), a glycoprotein that is anchored to the cell membrane by phosphatidylinositol, binds activated complement fragments C3b and C4b, thereby inhibiting amplification of the complement cascade on host cell membranes. Here, we report the molecular cloning of human DAF from HeLa cells. Analysis of DAF complementary DNAs revealed two classes of DAF messenger RNA, one apparently derived from the other by a splicing event that causes a coding frameshift near the C terminus. The apparent 'intron' sequence contains an Alu family member and encodes contiguous protein sequence. Two DAF proteins are therefore possible, having divergent C-terminal domains which differ in their hydrophobicity. Both mRNAs are found on polysomes, suggesting that both are translated. We propose that the major (90%) spliced DAF mRNA encodes membrane-bound DAF whereas the minor (10%) unspliced DAF mRNA may encode secreted DAF and we present expression data supporting this. The deduced DAF sequence contains four repeating units homologous to a consensus repeat found in a recently described family of complement proteins. 相似文献
2.
Raman lasers based on potassium gadolinium tungstate and lead tungstate crystals pumped by a≈120 ps Nd: YAG laser at 1.064/μm were developed. High reflection mirrors for the Stokes wavelength have been used to generate near-infrared and eye safe spectral region of 1.15 - 1.32/μm. Second harmonic generation of the generated Raman lasers was observed. Eifficient multiple Stokes and anti-Stokes picosecond generation in 64 crystals have been shown to exhibit stimulated Raman scattering on about 700 lines covering the whole visible and near-infrared spectrum. All stimulated Raman scattering (SRS) wavelengths in the visible and near-infrared spectrum are identified and attributed to the SRS-active vibration modes of these crystals. 相似文献
3.
CpG methylation is maintained in human cancer cells lacking DNMT1 总被引:31,自引:0,他引:31
Rhee I Jair KW Yen RW Lengauer C Herman JG Kinzler KW Vogelstein B Baylin SB Schuebel KE 《Nature》2000,404(6781):1003-1007
Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer; however, the mechanisms responsible for this aberrant methylation are poorly understood. The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible for most of the methylation of the human genome, including the abnormal methylation found in cancers. To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal carcinoma cells. Here we show that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation. Although juxtacentromeric satellites became significantly demethylated, most of the loci that we analysed, including the tumour suppressor gene p16INK4a, remained fully methylated and silenced. These results indicate that DNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DNMT1 can maintain the methylation of most of the genome. 相似文献
4.
Big data: The future of biocuration 总被引:2,自引:0,他引:2
Howe D Costanzo M Fey P Gojobori T Hannick L Hide W Hill DP Kania R Schaeffer M St Pierre S Twigger S White O Rhee SY 《Nature》2008,455(7209):47-50
5.
Patten IS Rana S Shahul S Rowe GC Jang C Liu L Hacker MR Rhee JS Mitchell J Mahmood F Hess P Farrell C Koulisis N Khankin EV Burke SD Tudorache I Bauersachs J del Monte F Hilfiker-Kleiner D Karumanchi SA Arany Z 《Nature》2012,485(7398):333-338
Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. 相似文献
6.
Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family 总被引:2,自引:0,他引:2
P R Schofield M G Darlison N Fujita D R Burt F A Stephenson H Rodriguez L M Rhee J Ramachandran V Reale T A Glencorse 《Nature》1987,328(6127):221-227
Amino-acid sequences derived from complementary DNAs encoding the alpha- and beta-subunits of the GABA/benzodiazepine receptor from bovine brain show homology with other ligand-gated receptor subunits, suggesting that there is a super-family of ion-channel-containing receptors. Co-expression of the in vitro-generated alpha-subunit and beta-subunit RNAs in Xenopus oocytes produces a functional receptor and ion channel with the pharmacological properties characteristic of the GABAA receptor. 相似文献
7.
8.
Structural and functional basis for GABAA receptor heterogeneity 总被引:37,自引:0,他引:37
E S Levitan P R Schofield D R Burt L M Rhee W Wisden M K?hler N Fujita H F Rodriguez A Stephenson M G Darlison 《Nature》1988,335(6185):76-79
When gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in vertebrate brain, binds to its receptor it activates a chloride channel. Neurotransmitter action at the GABAA receptor is potentiated by both benzodiazepines and barbiturates which are therapeutically useful drugs (reviewed in ref. 1). There is strong evidence that this receptor is heterogeneous. We have previously isolated complementary DNAs encoding an alpha- and a beta-subunit and shown that both are needed for expression of a functional GABAA receptor. We have now isolated cDNAs encoding two additional GABAA receptor alpha-subunits, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating a molecular basis for it. These alpha-subunits are differentially expressed within the CNS and produce, when expressed with the beta-subunit in Xenopus oocytes, receptor subtypes which can be distinguished by their apparent sensitivity to GABA. Highly homologous receptor subtypes which differ functionally seem to be a common feature of brain receptors. 相似文献
9.
Byunghyuk Kim Kyosun Park Kunsoo Rhee 《Cellular and molecular life sciences : CMLS》2013,70(15):2623-2636
The vast majority of mammalian testes are located outside the body cavity for proper thermoregulation. Heat has an adverse effect on mammalian spermatogenesis and eventually leads to sub- or infertility. Recent studies have provided insights into the molecular response of male germ cells to high temperatures. Here, we review the effects of heat on male germ cells and discuss the mechanisms underlying germ cell loss and impairment. We also discuss the role of translational control in male germ cells as a potential protective mechanism against heat-induced germ cell apoptosis. 相似文献
10.
Choi MH Lee IK Kim GW Kim BU Han YH Yu DY Park HS Kim KY Lee JS Choi C Bae YS Lee BI Rhee SG Kang SW 《Nature》2005,435(7040):347-353
Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H2O2 (refs 1, 2-3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H2O2 produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H2O2, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cgamma1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H2O2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease. 相似文献