Abstract:
:We have investigated the theory that the insulin-induced loss of insulin binding from adipocytes is due to internalization of insulin receptors. Cell-surface receptors were assessed by the binding capacity of intact cells at 16 degrees C. Total (i.e., cell-surface plus intracellular) receptors were assessed by solubilizing the cells in 1% Triton X-100 and then measuring binding by the solubilized extract. Intracellular receptors were measured by treating the cells with trypsin before solubilizing them. The trypsin treatment removed greater than 90% of the cell-surface binding, so that any significant binding by soluble extracts of these cells must represent intracellular receptors. Adipocytes were incubated with insulin (100 ng/ml) with or without chloroquine (0.2 mM) for 4 hr. Insulin alone resulted in a 62% loss of cell-surface receptors, but only a 46% loss of total receptors, and a 170% increase in intracellular receptors, suggesting that the lost cell-surface receptors were internalized, where some were degraded. Insulin in the presence of chloroquine resulted in a 34% loss of cell-surface receptors, but no loss of total receptors, and a 300% increase in intracellular receptors. Thus, in the presence of chloroquine receptors were internalized but not degraded. The loss of cell-surface receptors and appearance of intracellular receptors were time and dose dependent and were linearly related. These results demonstrate that insulin causes translocation of insulin receptors from the cell surface to the cell interior, where they can be degraded (or inactivated) by a chloroquine-sensitive process.
journal_name
Proc Natl Acad Sci U S Aauthors
Green A,Olefsky JMdoi
10.1073/pnas.79.2.427subject
Has Abstractpub_date
1982-01-01 00:00:00pages
427-31issue
2eissn
0027-8424issn
1091-6490journal_volume
79pub_type
杂志文章abstract::Interphotoreceptor retinoid-binding protein (IRBP) has been hypothesized to function as an intercellular shuttle in the vertebrate eye, serving to transport retinoids between the retinal pigment epithelium (RPE) and photoreceptors in the process by which visual pigment is regenerated after photolysis. This hypothesis ...
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.87.17.6907
更新日期:1990-09-01 00:00:00
abstract::The present study examined the social skills of previously institutionalized, 8-y-old Romanian children from the Bucharest Early Intervention Project and the influence of attachment security and brain electrical activity (alpha power) on these skills. Participants included children randomized to an intervention involv...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1121256109
更新日期:2012-10-16 00:00:00
abstract::Pulmonary pathologies including adult respiratory distress syndrome are characterized by disruption of pulmonary integrity and edema compromising respiratory function. Sphingosine 1-phosphate (S1P) is a lipid mediator synthesized and/or stored in mast cells, platelets, and epithelial cells, with production up-regulate...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,收录出版
doi:10.1073/pnas.0501997102
更新日期:2005-06-28 00:00:00
abstract::Lateral organ distribution at the shoot apical meristem defines specific and robust phyllotaxis patterns that have intrigued biologists and mathematicians for centuries. In silico studies have revealed that this self-organizing process can be recapitulated by modeling the polar transport of the phytohormone auxin. Phy...
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.1213497110
更新日期:2013-01-15 00:00:00
abstract::To elucidate the function of the two nerve growth factor (NGF) receptors, p75NGFR and p140trk, chimeric molecules were constructed of tumor necrosis factor (TNF) and NGF receptors. Rat PC12 pheochromocytoma cells transiently transfected with TNF-p140trk chimeras, which contain the extracellular domain of TNF receptor ...
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.90.18.8717
更新日期:1993-09-15 00:00:00
abstract::Cotransfection assays were used to show that the members of the GTP-binding protein Gq class of alpha subunits could activate phospholipase C (PLC) beta 2. Similar experiments also demonstrated that G beta 1 gamma 1, G beta 1 gamma 5, and G beta 2 gamma 5 could activate the beta 2 isoform of PLC but not the beta 1 iso...
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.90.11.5297
更新日期:1993-06-01 00:00:00
abstract::Neurophysiology is increasingly focused on identifying coincident activity among neurons. Strong inferences about neural computation are made from the results of such studies, so it is important that these results be accurate. However, the preliminary step in the analysis of such data, the assignment of spike waveform...
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.1115236109
更新日期:2012-05-08 00:00:00
abstract::Toll-like receptors (TLRs) play key roles in detecting pathogens and initiating inflammatory responses that, subsequently, prime specific adaptive responses. Several mechanisms control TLR activity to avoid excessive inflammation and consequent immunopathology, including the anti-inflammatory cytokine IL-10. Recently,...
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.1219852110
更新日期:2013-07-09 00:00:00
abstract::The topology of the tight junction is probed by introducing dipicrylamine (dpa-), a lipid-soluble anion, into the membranes of hepatocyte pairs in culture. Once partitioned into the membrane, dpa- ions are free to move in the hydrophobic core of the membrane, where their mobile charges greatly increase membrane capaci...
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.88.20.9365
更新日期:1991-10-15 00:00:00
abstract::Mapping posttranslational modifications (PTMs), which diversely modulate biological functions, represents a significant analytical challenge. The centerpiece technology for PTM site identification, mass spectrometry (MS), requires proteolytic cleavage in the vicinity of a PTM to yield peptides for sequencing. This req...
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.1609925113
更新日期:2016-12-20 00:00:00
abstract::BALB/c mice immunized with myeloma proteins 315 or 460 made antibodies to the individually specific ("idiotypic") determinants of these proteins and suppressed growth of the corresponding transplanted tumor cells (MOPC-315 or MOPC-460). Stable, variant MOPC-315 tumors that produce only the light chain of protein 315 g...
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.69.6.1540
更新日期:1972-06-01 00:00:00
abstract::Organic hydroperoxide resistance (Ohr) enzymes are unique Cys-based, lipoyl-dependent peroxidases. Here, we investigated the involvement of Ohr in bacterial responses toward distinct hydroperoxides. In silico results indicated that fatty acid (but not cholesterol) hydroperoxides docked well into the active site of Ohr...
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.1619659114
更新日期:2017-01-10 00:00:00
abstract::Immune responses of the malaria vector mosquito Anopheles gambiae were monitored systematically by the induced expression of five RNA markers after infection challenge. One newly isolated marker encodes a homologue of the moth Gram-negative bacteria-binding protein (GNBP), and another corresponds to a serine protease-...
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.94.21.11508
更新日期:1997-10-14 00:00:00
abstract::Biological polymers such as nucleic acids and proteins are constructed of only one-the d or l-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantio...
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.1603030113
更新日期:2016-06-14 00:00:00
abstract::The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we have made a recombinant fusion protein of SEA and the Fab region o...
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.91.19.8945
更新日期:1994-09-13 00:00:00
abstract::The human epidermal growth factor receptor 2 (HER2) is specifically overexpressed in tumors of several cancers, including an aggressive form of breast cancer. It is therefore a target for both cancer diagnostics and therapy. The 58 amino acid residue Zher2 affibody molecule was previously engineered as a high-affinity...
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.1005025107
更新日期:2010-08-24 00:00:00
abstract::Selection of aptamers from nucleic acid libraries by in vitro evolution represents a powerful method of identifying high-affinity ligands for a broad range of molecular targets. Nevertheless, a sizeable fraction of proteins remain difficult targets due to inherently limited chemical diversity of nucleic acids. We have...
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.1213933109
更新日期:2012-12-04 00:00:00
abstract::Standard economic and evolutionary models assume that humans are fundamentally selfish. On this view, any acts of prosociality--such as cooperation, giving, and other forms of altruism--result from covert attempts to avoid social injunctions against selfishness. However, even in the absence of social pressure, individ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
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更新日期:2011-12-06 00:00:00
abstract::Na(+)-channel inactivation is proposed to occur by binding of an intracellular inactivation gate to a hydrophobic inactivation gate receptor in the intracellular mouth of the pore. Amino acid residues in transmembrane segment S6 of domain IV (IVS6) that are critical for fast inactivation were identified by alanine-sca...
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.91.25.12346
更新日期:1994-12-06 00:00:00
abstract::The GTPase-activating protein (GAP) has been postulated to function either as a negative regulator or as a possible target protein of Ras in mammalian cells and Xenopus oocytes. Ras must be localized in the plasma membrane of vertebrate cells to function, but GAP is localized in the cytosol. To test whether Ras functi...
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.86.17.6630
更新日期:1989-09-01 00:00:00
abstract::Coherent oscillations in the theta-to-gamma frequency range have been proposed as a mechanism that coordinates neural activity in large-scale cortical networks in sensory, motor, and cognitive tasks. Whether this mechanism also involves coherent oscillations at delta frequencies (1-4 Hz) is not known. Rather, delta os...
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.1314681110
更新日期:2013-09-10 00:00:00
abstract::We used a high-titer recombinant adeno-associated virus (rAAV) vector to express WT or mutant human alpha-synuclein in the substantia nigra of adult marmosets. The alpha-synuclein protein was expressed in 90-95% of all nigral dopamine neurons and distributed by anterograde transport throughout their axonal and dendrit...
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.0536383100
更新日期:2003-03-04 00:00:00
abstract::The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen patte...
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.83.12.4394
更新日期:1986-06-01 00:00:00
abstract::Memory CD4(+) T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like struc...
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.1512600113
更新日期:2016-05-17 00:00:00
abstract::Biodistribution studies of a water-soluble radioactive metallofullerene compound have been conducted using BALB/c mice. To this end, a sample containing Hox@C82 (x = 1, 2) was purified and derivatized to prepare the water-soluble metallofullerol, Hox@C82(OH)y. This metallofullerol was then neutron-activated (165Ho[n,g...
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.96.9.5182
更新日期:1999-04-27 00:00:00
abstract::We have previously shown that surfactant protein A (SP-A) mediates in vitro killing of mycoplasmas by alveolar macrophages (AMs) from resistant C57BL/6 mice through a nitric oxide (.NO)-dependent mechanism. Herein, SP-A-deficient [SP-A(-/-)] and inducible.NO synthase-deficient [iNOS(-/-)] mice were infected intranasal...
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.96.9.4953
更新日期:1999-04-27 00:00:00
abstract::Polyploidy, which results from whole genome duplication (WGD), has shaped the long-term evolution of eukaryotic genomes in all kingdoms. Polyploidy is also implicated in adaptation, domestication, and speciation. Yet when WGD newly occurs, the resulting neopolyploids face numerous challenges. A particularly pernicious...
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.1919459117
更新日期:2020-04-21 00:00:00
abstract::Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here...
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.1801253115
更新日期:2018-07-24 00:00:00
abstract::Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insig...
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.0408170101
更新日期:2004-12-21 00:00:00
abstract::Recently, we described a recurrent variant translocation, t(11;17)(q23;q21), in acute promyelocytic leukemia (APL) which juxtaposes PLZF, a gene encoding a zinc finger protein, to RARA, encoding retinoic acid receptor alpha (RAR alpha). We have now cloned cDNAs encoding PLZF-RAR alpha chimeric proteins and studied the...
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.91.3.1178
更新日期:1994-02-01 00:00:00