Abstract:
:STAT1 is an essential transcription factor for macrophage activation by IFN-gamma and requires phosphorylation of the C-terminal Ser727 for transcriptional activity. In macrophages, Ser727 phosphorylation in response to bacterial lipopolysaccharide (LPS), UV irradiation, or TNF-alpha occurred through a signaling path sensitive to the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 whereas IFN-gamma-mediated Ser727 phosphorylation was not inhibited by the drug. Consistently, SB203580 did not affect IFN-gamma-mediated, Stat1-dependent transcription but inhibited its enhancement by LPS. Furthermore, LPS, UV irradiation, and TNF-alpha caused activation of p38 MAPK whereas IFN-gamma did not. An essential role for p38 MAPK activity in STAT1 Ser727 phosphorylation was confirmed by using cells expressing an SB203580-resistant p38 MAPK. In such cells, STAT1 Ser727 phosphorylation in response to UV irradiation was found to be SB203580 insensitive. Targeted disruption of the mapkap-k2 gene, encoding a kinase downstream of p38 MAPK with a key role in LPS-stimulated TNF-alpha production and stress-induced heat shock protein 25 phosphorylation, was without a significant effect on UV-mediated Ser727 phosphorylation. The recombinant Stat1 C terminus was phosphorylated in vitro by p38MAPKalpha and beta but not by MAPK-activated protein kinase 2. Janus kinase 2 activity, previously reported to be required for IFN-gamma-mediated Ser727 phosphorylation, was not needed for LPS-mediated Ser727 phosphorylation, and activation of Janus kinase 2 did not cause the appearance of STAT1 Ser727 kinase activity. Our data suggest that STAT1 is phosphorylated at Ser727 by a stress-activated signaling pathway either through p38 MAPK directly or through an unidentified kinase downstream of p38MAPK.
journal_name
Proc Natl Acad Sci U S Aauthors
Kovarik P,Stoiber D,Eyers PA,Menghini R,Neininger A,Gaestel M,Cohen P,Decker Tdoi
10.1073/pnas.96.24.13956keywords:
subject
Has Abstractpub_date
1999-11-23 00:00:00pages
13956-61issue
24eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::The completion of the human genome project and the development of high-throughput approaches herald a dramatic acceleration in the pace of biological research. One of the most compelling next steps will be learning the functional roles of all proteins. Achievement of this goal depends in part on the rapid expression a...
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.042684199
更新日期:2002-03-05 00:00:00
abstract::Although soft devices (grippers, actuators, and elementary robots) are rapidly becoming an integral part of the broad field of robotics, autonomy for completely soft devices has only begun to be developed. Adaptation of conventional systems of control to soft devices requires hard valves and electronic controls. This ...
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.1820672116
更新日期:2019-04-16 00:00:00
abstract::Lethal factor, the principal virulence factor of Bacillus anthracis, inhibits mitogen-activated protein kinase (MAPK) signaling by proteolytically cleaving MAPK kinases. Edema factor, another component of anthrax toxin, is an adenylate cyclase, which increases intracellular cAMP. Inhibition of MAPK signaling with eith...
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.052707699
更新日期:2002-03-05 00:00:00
abstract::The configuration of the heme-carbonyl group upon binding of carbon monoxide to sperm whale myoglobin (Mb) in crystals is evaluated on the basis of infrared spectroscopic methods. Multiplets of the totally symmetric C-O stretching mode are observed for the heme-bound ligand near 1933, 1944, and 1967 cm-1, correspondin...
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.76.12.6042
更新日期:1979-12-01 00:00:00
abstract::The helicity in water has been determined for several series of alanine-rich peptides that contain single lysine residues and that are N-terminally linked to a helix-inducing and reporting template termed Ac-Hel1. The helix-propagating constant for alanine (sAla value) that best fits the properties of these peptides l...
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.93.9.4025
更新日期:1996-04-30 00:00:00
abstract::Although the occurrence of epistasis and pleiotropy is widely accepted at the molecular level, its effect on the adaptive value of fitness-related genes is rarely investigated in plants. Knowledge of these features of a gene is critical to understand the molecular basis of adaptive evolution. Here we investigate the i...
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.0708209104
更新日期:2007-10-23 00:00:00
abstract::During cell division, the mitotic spindle segregates the sister chromatids into two nascent cells, such that each daughter cell inherits one complete set of chromosomes. Errors in spindle formation can result in both chromosome missegregation and cytokinesis defects and hence lead to genomic instability. To ensure 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.0507066103
更新日期:2006-04-04 00:00:00
abstract::The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subjec...
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.90.8.3710
更新日期:1993-04-15 00:00:00
abstract::The nucleus accumbens is a brain region in which limbic and motor inputs converge. How these information modalities shape accumbens output is not clearly understood. Here, we report that synaptic inputs from the prefrontal cortex and limbic structures interact differently depending on their timing. Coincident inputs 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.202303199
更新日期:2002-10-01 00:00:00
abstract::The method presented here refines molecular conformations directly against projections of single particles measured by electron microscopy. By optimizing the orientation of the projection at the same time as the conformation, the method is well-suited to two-dimensional class averages from cryoelectron microscopy. Suc...
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.1205945109
更新日期:2012-06-19 00:00:00
abstract::Acquisition of acetylcholine receptors during differentiation of a clonal myoblast cell line was monitored with a neurotoxin isolated from venom of the Indian Cobra Naja naja. Toxin bound specifically and reversibly to acetylcholine receptors of the differentiated cells. Specificity of the binding reaction was assayed...
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.69.10.2762
更新日期:1972-10-01 00:00:00
abstract::The sequences of large insert clones containing genomic DNA that is orthologous to the maize adh1 region were obtained for sorghum, rice, and the adh1-homoeologous region of maize, a remnant of the tetraploid history of the Zea lineage. By using all four genomes, it was possible to describe the nature, timing, and lin...
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.1434476100
更新日期:2003-10-14 00:00:00
abstract::Whether electromagnetic precursors to earthquakes (EQs) exist is an important question not only for EQ prediction but also for understanding the physical processes of EQ generation. Slow transient geoelectric potential changes have been observed before several recent EQs in Japan. In most cases, they appeared 1-19 day...
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.97.9.4561
更新日期:2000-04-25 00:00:00
abstract::The regulation of protein function through ligand-induced conformational changes is crucial for many signal transduction processes. The binding of a ligand alters the delicate energy balance within the protein structure, eventually leading to such conformational changes. In this study, we elucidate the energetic and 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.1504625112
更新日期:2015-08-18 00:00:00
abstract::Complementation of the plasmin fragments of reduced-carbamoylmethylated (Cam) human somatotropin (hGH) with those of reduced-carbamoylmethylated human chorionic somatomammotropin (hCS) have been investigated. It was found that the recombinant obtained by noncovalent interaction of [Cys(Cam)53]hGH-(1-134) with [Cys(Cam...
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.75.4.1700
更新日期:1978-04-01 00:00:00
abstract::The catalytic activity of low-dimensional electrocatalysts is highly dependent on their local atomic structures, particularly those less-coordinated sites found at edges and corners; therefore, a direct probe of the electrocatalytic current at specified local sites with true nanoscopic resolution has become critically...
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.1821091116
更新日期:2019-06-11 00:00:00
abstract::Sparse 3T3 cells, in excess serum, become quiescent in the early G(1) (or G(0)) phase of the cell cycle if the cells are cultured in low concentrations of amino acids, glucose, or phosphate ion. These quiescent cells then initiate DNA synthesis if the concentration of the limiting nutrient is increased. In normal medi...
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.71.8.2942
更新日期:1974-08-01 00:00:00
abstract::The RNA-directed DNA polymerase (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase EC 2.7.7.7) of avian oncornavirus requires a tryptophan tRNA (tRNATrp) primer molecule located close to the 5' end of the viral RNA genome for the initiation of DNA synthesis in vitro. In this communication we demonstrate that...
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.73.4.1329
更新日期:1976-04-01 00:00:00
abstract::In isogamous species of Chlamydomonas, such as Chlamydomonas reinhardtii and Chlamydomonas eugametos, the sexual process involves the use of flagella agglutinins by which the gametes of compatible strains adhere through chance encounter and ultimately pair and fuse to form zygotes. In a newly described heterogamous sp...
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.92.2.641
更新日期:1995-01-17 00:00:00
abstract::Outer membrane protein (OMP) biogenesis is critical to bacterial physiology because the cellular envelope is vital to bacterial pathogenesis and antibiotic resistance. The process of OMP biogenesis has been studied in vivo, and each of its components has been studied in isolation in vitro. This work integrates paramet...
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.1601002113
更新日期:2016-08-16 00:00:00
abstract::Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be caused by failure in n...
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.88.8.3402
更新日期:1991-04-15 00:00:00
abstract::Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in 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.2016650117
更新日期:2020-11-10 00:00:00
abstract::We describe here a third region of variability in human fibronectin (FN) due to alternative RNA splicing. Two other positions of alternative splicing have been reported previously (ED and IIICS). The third region involves a 273-nucleotide exon encoding exactly one 91-amino acid repeat of type III homology, located bet...
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.84.20.7179
更新日期:1987-10-01 00:00:00
abstract::Skeletal muscle adapts to different patterns of motor nerve activity by alterations in gene expression that match specialized properties of contraction, metabolism, and muscle mass to changing work demands (muscle plasticity). Calcineurin, a calcium/calmodulin-dependent, serine-threonine protein phosphatase, has been ...
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.0308179101
更新日期:2004-06-22 00:00:00
abstract::Sympathetic activation of β-adrenoreceptors (β-AR) represents a hallmark in the development of heart failure (HF). However, little is known about the underlying mechanisms of gene regulation. In human ventricular myocardium from patients with end-stage HF, we found high levels of phosphorylated histone 3 at serine-28 ...
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.1816521116
更新日期:2019-10-29 00:00:00
abstract::Many Drosophila non-long terminal repeat (LTR) retrotransposons actively transpose into internal, gene-rich regions of chromosomes but do not transpose onto chromosome ends. HeT-A and TART are remarkable exceptions; they form telomeres of Drosophila by repeated transpositions onto the ends of chromosomes and never tra...
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.032071999
更新日期:2002-03-19 00:00:00
abstract::Analysis of the nucleotide and deduced amino acid sequences of the biologically active mouse mdr1 cDNA clone indicates that the protein is formed by two highly homologous halves, each containing six putative transmembrane domains and a nucleotide-binding site. The duplicated unit shows high sequence homology to the pr...
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.86.17.6488
更新日期:1989-09-01 00:00:00
abstract::Two major DNA double-strand break repair pathways exist in all eukaryotes, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR). Although both pathways can function throughout the cell cycle, NHEJ predominates in G0/G1) (when a replicated sister chromatid is unavailable), whereas HR makes a more subs...
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.0406466102
更新日期:2005-02-01 00:00:00
abstract::The spatiotemporal regulation of neurotransmitter transporters involves proteins that interact with their intracellular domains. Using a proteomic approach, we identified several proteins that interact with the C terminus of the serotonin transporter (SERT). These included neuronal nitric oxide synthase (nNOS), a PSD-...
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.0610964104
更新日期:2007-05-08 00:00:00
abstract::Swarming bacteria move in multicellular groups and exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. We find that high densities promote bacterial survival, even ...
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.0910934107
更新日期:2010-02-23 00:00:00