Abstract:
:Although Hsp90 displays general chaperone activity in vitro, few substrates of the chaperone have been identified in vivo, and the characteristics that render these substrates dependent on Hsp90 remain elusive. To investigate this issue, we exploited a paradoxical observation: several unrelated oncogenic viral tyrosine kinases, including v-src, attain their native conformation after association with Hsp90, yet their nearly identical cellular homologs interact only weakly with the chaperone. It has been controversial whether Hsp90 is vital for normal maturation of the cellular kinases or is simply binding a misfolded subfraction of the proteins. By modulating Hsp90 levels in Saccharomyces cerevisiae, we determined that Hsp90 is indeed necessary for the maturation of c-src (the normal homolog of v-src). c-src maturation is, however, less sensitive to Hsp90 perturbations than is v-src maturation. Dependence of the two proteins on Hsp90 does not correspond to their relative efficiency in reaching their final destination (the plasma membrane); we observed that in yeast, unlike in vertebrate cells, neither c-src nor v-src concentrate in the membrane. Expression of different v/c-src chimeras in cells carrying wild-type or temperature-sensitive Hsp90 alleles revealed that the difference between the proteins instead arises from multiple, naturally occurring mutations in the C-terminal region of v-src.
journal_name
Proc Natl Acad Sci U S Aauthors
Xu Y,Singer MA,Lindquist Sdoi
10.1073/pnas.96.1.109subject
Has Abstractpub_date
1999-01-05 00:00:00pages
109-14issue
1eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::Under conditions (0.2% CO2; 1% O2) that allow high rates of photosynthesis, chlorophyll fluorescence was measured simultaneously with carbon assimilation at various light intensities in spinach (Spinacia oleracea) leaves. Using a stoichiometry of 3 ATP/CO2 and the known relationship between ATP synthesis rate and driv...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.26.12185
更新日期:1995-12-19 00:00:00
abstract::Antigen.antibody complexes (Ag.Ab) prepared from (125)I-labeled bovine serum albumin and guinea pig anti-albumin were incubated at 37 degrees C for 30 min with normal human serum diluted optimally for binding (1:16) and then with autologous erythrocytes (RBC). After washing, RBC-bearing antigen.antibody.complement com...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.16.5047
更新日期:1982-08-01 00:00:00
abstract::The primary structure of about half of the protein chain of yeast alcohol dehydrogenase has been determined and compared with the amino-acid sequences of other dehydrogenases. The enzyme is found to be distantly related to horse-liver alcohol dehydrogenase, although these two proteins have different quaternary structu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.8.2295
更新日期:1973-08-01 00:00:00
abstract::Although sunlight provides the energy necessary for plants to survive and grow, light can also damage reaction centers of photosystem II (PSII) and reduce photochemical efficiency. To prevent damage, plants possess photoprotective mechanisms that dissipate excess excitation. A subset of these mechanisms is collectivel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1704373114
更新日期:2017-08-15 00:00:00
abstract::In this study, a comparative analysis of metal-related neuronal vulnerability was performed in two brainstem nuclei, the locus coeruleus (LC) and substantia nigra (SN), known targets of the etiological noxae in Parkinson's disease and related disorders. LC and SN pars compacta neurons both degenerate in Parkinson's di...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0403495101
更新日期:2004-06-29 00:00:00
abstract::The feasibility of long-term information storage by brain type II Ca2+/calmodulin-dependent protein kinase molecules is explored. Recent evidence indicates that this protein has switch-like properties. Equations are derived showing that a single kinase holoenzyme could form a bistable switch having the stability neces...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.14.5320
更新日期:1988-07-01 00:00:00
abstract::A major part of the present understanding of the molecular basis of signal transduction has been gained from in vitro studies using classical biochemical methods. In this study, we used 31P NMR spectroscopy to investigate the response of live M2R mouse melanoma cells to stimulation by melanocyte-stimulating hormone (M...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.4.1506
更新日期:1991-02-15 00:00:00
abstract::Protein sequences are often highly redundant and evolution can change them beyond recognition. It can therefore be difficult to identify proteins with functional or structural similarities by inspection of their sequences. Here we have used an experimental evolutionary approach to detect hidden similarities between th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2134365100
更新日期:2003-11-11 00:00:00
abstract::Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.6.3194
更新日期:1999-03-16 00:00:00
abstract::The nitrogen isotopic composition (15N/14N) of forested ecosystems varies systematically worldwide. In tropical forests, which are elevated in 15N relative to temperate biomes, a decrease in ecosystem 15N/14N with increasing rainfall has been reported. This trend is seen in a set of well characterized Hawaiian rainfor...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0510185103
更新日期:2006-06-06 00:00:00
abstract::Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-ser...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.9.3948
更新日期:1995-04-25 00:00:00
abstract::Neural crest cell derivatives have been suggested to be involved in thymus development. We established nonlymphoid thymic stromal cell cultures capable of supporting T-cell differentiation. In these nonlymphoid cell cultures, we identified cells with phenotypic and biochemical markers specific for neuronal cells. Neur...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.8.3209
更新日期:1992-04-15 00:00:00
abstract::Human populations have undergone dramatic expansions in size, but other than the growth associated with agriculture, the dates and magnitudes of those expansions have never been resolved. Here, we introduce two new statistical tests for population expansion, which use variation at a number of unlinked genetic markers ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.14.8119
更新日期:1998-07-07 00:00:00
abstract::Copper is an essential micronutrient that plays a central role for a broad range of biological processes. Although there is compelling evidence that the intracellular milieu does not contain any free copper ions, the rapid kinetics of copper uptake and release suggests the presence of a labile intracellular copper poo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0406547102
更新日期:2005-08-09 00:00:00
abstract::We have cloned two species of EcoRI-cleaved DNA segments that together cover the entire sequence for the human interleukin 2 gene and have determined the nucleotide sequence of the gene and its flanking regions. The gene contains three introns and the exon sequences can be aligned with the previously reported cDNA seq...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.24.7437
更新日期:1983-12-01 00:00:00
abstract::Dendritic spines receive most synaptic inputs in the forebrain. Their morphology, with a spine head isolated from the dendrite by a slender neck, indicates a potential role in isolating inputs. Indeed, biochemical compartmentalization occurs at spine heads because of the diffusional bottleneck created by the spine nec...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0608755103
更新日期:2006-11-21 00:00:00
abstract::The study of photoinitiated electron transfer in donor-bridge-acceptor molecules has helped elucidate the distance dependence of electron transfer rates and behavior of various electron transfer mechanisms. In all reported cases, the energies of the bridge electronic states involved in the electron transfer change dra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0408940102
更新日期:2005-03-08 00:00:00
abstract::A direct method for the determination of N-linked glycosylation sites in highly glycosylated proteins is described. Carcinoembryonic antigen (CEA) and a nonspecific crossreacting antigen (NCA) were chemically deglycosylated, and peptide maps were prepared by reverse-phase HPLC. The peptides were sequenced on a gas-pha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.4.920
更新日期:1987-02-01 00:00:00
abstract::A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1013699108
更新日期:2011-02-22 00:00:00
abstract::The time-dependent Schrödinger equation is a cornerstone of quantum physics and governs all phenomena of the microscopic world. However, despite its importance, its origin is still not widely appreciated and properly understood. We obtain the Schrödinger equation from a mathematical identity by a slight generalization...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1302475110
更新日期:2013-04-02 00:00:00
abstract::Phosphocholine (PC) is an abundant primary form of organic phosphate that is transported in plant xylem sap. Addition of PC to the perfusate of compressed Pi-starved sycamore cells monitored by 31P NMR spectroscopy resulted in an accumulation of PC and all the other phosphate esters in the cytoplasmic compartment. Add...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.11.4280
更新日期:1990-06-01 00:00:00
abstract::Vesicles were constituted with glycophorin, the Sendai virus receptor of human erythrocytes, and loaded with calcein, a polar derivative of fluorescein, at self-quenching concentrations. On exposure to Sendai virus and mild hypo-osmotic stress, vesicles of the appropriate composition released a significant portion of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.6.1608
更新日期:1983-03-01 00:00:00
abstract::Whether mitotic structures like the centrosome can self-organize from the regulated mobility of their dynamic protein components remains unclear. Here, we combine fluorescence spectroscopy and chemical genetics to study in living cells the diffusion of polo-like kinase 1 (PLK1), an enzyme critical for centrosome matur...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1101112108
更新日期:2011-05-31 00:00:00
abstract::The sequence of a nucleotide region of f1 bacteriophage was determined on a bonded ultrathin acrylamide gel with a discontinuous buffer system by using the dideoxy-DNA sequencing method. This sequence and one other were analyzed for maximal base pairing with tRNAs. The results allow a prediction of the direction and p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.6.3539
更新日期:1980-06-01 00:00:00
abstract::Kinetics of growth and decay of triplet states of molecules at known orientation in a magnetic field have been measured. Amplitudes of the zero field eigenstates in each of the eigenstates at finite field were varied by choice of orientation. No interference between the amplitudes of the zero field states was found in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.11.4203
更新日期:1975-11-01 00:00:00
abstract::Antidiuretic hormone (ADH) increases the water permeability of the toad urinary bladder. The increase occurs in the apical plasma membrane of granular cells that line the urinary surface of the bladder and is produced by the insertion of water permeability units that have been identified by freeze-fracture electron mi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.6.1942
更新日期:1988-03-01 00:00:00
abstract::Poly(A)-containing RNA was isolated from ovaries of Xenopus laevis laevis and Triturus cristatus carnifex and used as a template for the synthesis of radioactive complementary DNA with RNA-dependent DNA polymerase. When annealed with an excess of homologous DNA, the complementary DNA is rendered double-stranded with k...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.9.3746
更新日期:1974-09-01 00:00:00
abstract::Forests and their soils contain the majority of the earth's terrestrial carbon stocks. Changes in patterns of tree growth can have a huge impact on atmospheric cycles, biogeochemical cycles, climate change, and biodiversity. Recent studies have shown increases in biomass across many forest types. This increase has bee...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0912376107
更新日期:2010-02-23 00:00:00
abstract::Mechanisms of estrogen-induced tumorigenesis in the target organ are not well understood. It has been suggested that oxidative stress resulting from metabolic activation of carcinogenic estrogens plays a critical role in estrogen-induced carcinogenesis. We tested this hypothesis by using an estrogen-induced hamster re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0437929100
更新日期:2003-04-01 00:00:00
abstract::The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. W...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619735114
更新日期:2017-01-17 00:00:00