当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > A dual role for the kinase-like domain of the tyrosine kinase Tyk2 in interferon-alpha signaling.

A dual role for the kinase-like domain of the tyrosine kinase Tyk2 in interferon-alpha signaling.

Abstract：

:Tyrosine kinases of the Janus kinase family initiate cellular responses through their association with receptors for alpha-helical cytokines. In addition to a tyrosine kinase domain, these enzymes possess a kinase-like (KL) domain, whose function remains elusive. To investigate the role of the KL domain of Tyk2 in interferon-alpha/beta signaling, we transfected a library of Tyk2 cDNAs containing random point mutations in KL into Tyk2-negative cells and selected for loss-of-function Tyk2 mutants. Four such mutants, V584D, G596V, H669P, and R856G, were identified through this screen. Like the wild-type Tyk2, the mutant proteins were able to sustain the level of IFNAR1 receptor protein. However, all four mutants were incapable of restoring high-affinity interferon-alpha binding in Tyk2-negative cells and were also catalytically impaired, even when transiently overexpressed. Interferon-alpha induced phosphorylation, and gene expression could be detected in V584D- or G596V-expressing cells, but not in H669P- or R856G-expressing cells. Furthermore, H669P and R856G proteins were constitutively highly phosphorylated. All together, our findings demonstrate that an intact KL domain is essential for the intrinsic catalytic activity of Tyk2 and for the establishment of a high-affinity interferon-alpha receptor complex.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Yeh TC,Dondi E,Uze G,Pellegrini S

doi

10.1073/pnas.160130297

keywords:

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

8991-6

issue

16

eissn

0027-8424

issn

1091-6490

pii

160130297

journal_volume

97

pub_type

杂志文章

相关文献

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA文献大全
  • Dipoles localized at helix termini of proteins stabilize charges.

    abstract：:The charge-stabilization effect associated with alpha-helices in proteins has been reexamined by microscopic calculations without any a priori assumptions about the dielectric constant of the protein. The calculations reproduce the observed charge stabilization effect of a helix in two well-defined test cases: a histi...

    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.88.5.2026

    authors： Aqvist J,Luecke H,Quiocho FA,Warshel A

    更新日期：1991-03-01 00:00:00

  • Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

    abstract：:RPE65 is a protein of unknown function expressed specifically by the retinal pigment epithelium. We examined all 14 exons of this gene in 147 unrelated patients with autosomal recessive retinitis pigmentosa (RP), in 15 patients with isolate RP, and in 45 patients with Leber congenital amaurosis (LCA). Sequence anomali...

    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.95.6.3088

    authors： Morimura H,Fishman GA,Grover SA,Fulton AB,Berson EL,Dryja TP

    更新日期：1998-03-17 00:00:00

  • Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.

    abstract：:Autocatalytic activation of an initiator caspase triggers the onset of apoptosis. In dying cells, caspase-9 activation is mediated by a multimeric adaptor complex known as the Apaf-1 apoptosome. The molecular mechanism by which caspase-9 is activated by the Apaf-1 apoptosome remains largely unknown. Here we demonstrat...

    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.1418000111

    authors： Hu Q,Wu D,Chen W,Yan Z,Yan C,He T,Liang Q,Shi Y

    更新日期：2014-11-18 00:00:00

  • Quantifying structure and performance diversity for sets of small molecules comprising small-molecule screening collections.

    abstract：:Using a diverse collection of small molecules we recently found that compound sets from different sources (commercial; academic; natural) have different protein-binding behaviors, and these behaviors correlate with trends in stereochemical complexity for these compound sets. These results lend insight into structural ...

    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.1015024108

    authors： Clemons PA,Wilson JA,Dančík V,Muller S,Carrinski HA,Wagner BK,Koehler AN,Schreiber SL

    更新日期：2011-04-26 00:00:00

  • Isolation and mapping of plasmids containing the Salmonella typhimurium origin of DNA replication.

    abstract：:A purified EcoRI restriction endonuclease fragment that determines resistance to kanamycin and is incapable of self-replication was used to select autonomously replicating fragments from an EcoRI digest of a Salmonella typhimurium F' plasmid containing the chromosomal region believed to include the S. typhimurium orig...

    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.76.7.3097

    authors： Zyskind JW,Deen LT,Smith DW

    更新日期：1979-07-01 00:00:00

  • Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells.

    abstract：:The present studies were conducted to determine whether prostaglandin F2 alpha (PGF2 alpha) stimulates the production of "second messengers" derived from inositol phospholipid hydrolysis and increases intracellular free Ca2+ ([Ca2+]i) in isolated bovine luteal cells. PGF2 alpha provoked rapid (10 sec) and sustained (u...

    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.84.11.3728

    authors： Davis JS,Weakland LL,Weiland DA,Farese RV,West LA

    更新日期：1987-06-01 00:00:00

  • Thermus thermophilus: a link in evolution of the tRNA-dependent amino acid amidation pathways.

    abstract：:Thermus thermophilus possesses an aspartyl-tRNA synthetase (AspRS2) able to aspartylate efficiently tRNAAsp and tRNAAsn. Aspartate mischarged on tRNAAsn then is converted into asparagine by an omega amidase that differs structurally from all known asparagine synthetases. However, aspartate is not misincorporated into ...

    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.95.22.12832

    authors： Becker HD,Kern D

    更新日期：1998-10-27 00:00:00

  • Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.

    abstract：:Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) ...

    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.1222433110

    authors： Swietach P,Youm JB,Saegusa N,Leem CH,Spitzer KW,Vaughan-Jones RD

    更新日期：2013-05-28 00:00:00

  • Type IV pili interactions promote intercellular association and moderate swarming of Pseudomonas aeruginosa.

    abstract：:Pseudomonas aeruginosa is a ubiquitous bacterium that survives in many environments, including as an acute and chronic pathogen in humans. Substantial evidence shows that P. aeruginosa behavior is affected by its motility, and appendages known as flagella and type IV pili (TFP) are known to confer such motility. The r...

    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.1414661111

    authors： Anyan ME,Amiri A,Harvey CW,Tierra G,Morales-Soto N,Driscoll CM,Alber MS,Shrout JD

    更新日期：2014-12-16 00:00:00

  • Transport properties of glass-forming liquids suggest that dynamic crossover temperature is as important as the glass transition temperature.

    abstract：:It is becoming common practice to partition glass-forming liquids into two classes based on the dependence of the shear viscosity η on temperature T. In an Arrhenius plot, ln η vs 1/T, a strong liquid shows linear behavior whereas a fragile liquid exhibits an upward curvature [super-Arrhenius (SA) behavior], a situati...

    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.1015340107

    authors： Mallamace F,Branca C,Corsaro C,Leone N,Spooren J,Chen SH,Stanley HE

    更新日期：2010-12-28 00:00:00

  • Surface chemical heterogeneity modulates silica surface hydration.

    abstract：:An in-depth knowledge of the interaction of water with amorphous silica is critical to fundamental studies of interfacial hydration water, as well as to industrial processes such as catalysis, nanofabrication, and chromatography. Silica has a tunable surface comprising hydrophilic silanol groups and moderately hydroph...

    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.1722263115

    authors： Schrader AM,Monroe JI,Sheil R,Dobbs HA,Keller TJ,Li Y,Jain S,Shell MS,Israelachvili JN,Han S

    更新日期：2018-03-20 00:00:00

  • Lagging adaptation to warming climate in Arabidopsis thaliana.

    abstract：:If climate change outpaces the rate of adaptive evolution within a site, populations previously well adapted to local conditions may decline or disappear, and banked seeds from those populations will be unsuitable for restoring them. However, if such adaptational lag has occurred, immigrants from historically warmer c...

    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.1406314111

    authors： Wilczek AM,Cooper MD,Korves TM,Schmitt J

    更新日期：2014-06-03 00:00:00

  • CXCR4 utilization is sufficient to trigger CD4+ T cell depletion in HIV-1-infected human lymphoid tissue.

    abstract：:The human chemokine receptors CCR5 and CXCR4 have emerged as the predominant cofactors, along with CD4, for cellular entry of HIV-1 in vivo whereas the contribution of other chemokine receptors to HIV disease has not been yet determined. CCR5-specific (R5) viruses predominate during primary HIV-1 infection whereas vir...

    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.96.2.663

    authors： Penn ML,Grivel JC,Schramm B,Goldsmith MA,Margolis L

    更新日期：1999-01-19 00:00:00

  • UV wavelength-dependent regulation of transcription-coupled nucleotide excision repair in p53-deficient human cells.

    abstract：:Nucleotide excision repair (NER) prevents skin cancer by eliminating highly genotoxic cyclobutane pyrimidine dimers (CPDs) induced in DNA by the UVB component of sunlight. NER consists of two distinct but overlapping subpathways, i.e., global NER, which removes CPD from the genome overall, and transcription-coupled NE...

    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.1232161100

    authors： Mathonnet G,Leger C,Desnoyers J,Drouin R,Therrien JP,Drobetsky EA

    更新日期：2003-06-10 00:00:00

  • De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis.

    abstract：:The 89-kDa cell surface glycoprotein, P3.58, is detectable on advanced human melanomas in situ but not on benign melanocytes or early melanomas. cDNA cloning of P3.58 from melanoma cells was accomplished by screening a lambda zap expression vector library with monoclonal antibodies produced against the denatured antig...

    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.86.2.641

    authors： Johnson JP,Stade BG,Holzmann B,Schwäble W,Riethmüller G

    更新日期：1989-01-01 00:00:00

  • Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons.

    abstract：:To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi, we evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide was ...

    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.88.4.1177

    authors： Cadroy Y,Maraganore JM,Hanson SR,Harker LA

    更新日期：1991-02-15 00:00:00

  • Differences in spontaneous mutation frequencies as a function of environmental stress in soil fungi at "Evolution Canyon," Israel.

    abstract：:When various wild strains of Penicillium lanosum and Aspergillus niger were placed in the same mild laboratory environment, their frequencies of new spontaneous mutations were clearly related to whether they had been isolated from a region of high or low microclimatic stress. In the mild environment, the total frequen...

    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.0801995105

    authors： Lamb BC,Mandaokar S,Bahsoun B,Grishkan I,Nevo E

    更新日期：2008-04-15 00:00:00

  • Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.

    abstract：:Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synt...

    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.92.11.4778

    authors： Sugawara T,Holt JA,Driscoll D,Strauss JF 3rd,Lin D,Miller WL,Patterson D,Clancy KP,Hart IM,Clark BJ

    更新日期：1995-05-23 00:00:00

  • Structural basis for efficient phosphorylation of 3'-azidothymidine monophosphate by Escherichia coli thymidylate kinase.

    abstract：:The crystal structures of Escherichia coli thymidylate kinase (TmpK) in complex with P1-(5'-adenosyl)-P5-(5'-thymidyl)pentaphosphate and P1-(5'-adenosyl)P5-[5'-(3'-azido-3'-deoxythymidine)] pentaphosphate have been solved to 2.0-A and 2.2-A resolution, respectively. The overall structure of the bacterial TmpK is very ...

    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.95.24.14045

    authors： Lavie A,Ostermann N,Brundiers R,Goody RS,Reinstein J,Konrad M,Schlichting I

    更新日期：1998-11-24 00:00:00

  • Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex.

    abstract：:We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the dorsolateral prefrontal cortex (dlPFC) in ovariectomized (OVX) female rhesus monkeys, and that E induces a corresponding increase in spine density in layer III dlPFC pyramidal neuro...

    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.0704757104

    authors： Hao J,Rapp PR,Janssen WG,Lou W,Lasley BL,Hof PR,Morrison JH

    更新日期：2007-07-03 00:00:00

  • Identifying the fundamental units of bacterial diversity: a paradigm shift to incorporate ecology into bacterial systematics.

    abstract：:The central questions of bacterial ecology and evolution require a method to consistently demarcate, from the vast and diverse set of bacterial cells within a natural community, the groups playing ecologically distinct roles (ecotypes). Because of a lack of theory-based guidelines, current methods in bacterial systema...

    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.0712205105

    authors： Koeppel A,Perry EB,Sikorski J,Krizanc D,Warner A,Ward DM,Rooney AP,Brambilla E,Connor N,Ratcliff RM,Nevo E,Cohan FM

    更新日期：2008-02-19 00:00:00

  • Origin of the p-process radionuclides 92Nb and 146Sm in the early solar system and inferences on the birth of the Sun.

    abstract：:The abundances of (92)Nb and (146)Sm in the early solar system are determined from meteoritic analysis, and their stellar production is attributed to the p process. We investigate if their origin from thermonuclear supernovae deriving from the explosion of white dwarfs with mass above the Chandrasekhar limit is in agr...

    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.1519344113

    authors： Lugaro M,Pignatari M,Ott U,Zuber K,Travaglio C,Gyürky G,Fülöp Z

    更新日期：2016-01-26 00:00:00

  • Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain.

    abstract：:Niemann-Pick type C (NPC) 1 protein plays important roles in moving cholesterol and other lipids out of late endosomes by means of vesicular trafficking, but it is not known whether NPC1 directly interacts with cholesterol. We performed photoaffinity labeling of intact cells expressing fluorescent protein (FP)-tagged ...

    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.0405255101

    authors： Ohgami N,Ko DC,Thomas M,Scott MP,Chang CC,Chang TY

    更新日期：2004-08-24 00:00:00

  • Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia.

    abstract：:Impaired magnesium reabsorption in patients with TRPM6 gene mutations stresses an important role of TRPM6 (melastatin-related TRP cation channel) in epithelial magnesium transport. While attempting to isolate full-length TRPM6, we found that the human TRPM6 gene encodes multiple mRNA isoforms. Full-length TRPM6 varian...

    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.0305252101

    authors： Chubanov V,Waldegger S,Mederos y Schnitzler M,Vitzthum H,Sassen MC,Seyberth HW,Konrad M,Gudermann T

    更新日期：2004-03-02 00:00:00

  • Accumulation of formamide in hydrothermal pores to form prebiotic nucleobases.

    abstract：:Formamide is one of the important compounds from which prebiotic molecules can be synthesized, provided that its concentration is sufficiently high. For nucleotides and short DNA strands, it has been shown that a high degree of accumulation in hydrothermal pores occurs, so that temperature gradients might play a role ...

    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.1600275113

    authors： Niether D,Afanasenkau D,Dhont JK,Wiegand S

    更新日期：2016-04-19 00:00:00

  • New HST data and modeling reveal a massive planetesimal collision around Fomalhaut.

    abstract：:The apparent detection of an exoplanet orbiting Fomalhaut was announced in 2008. However, subsequent observations of Fomalhaut b raised questions about its status: Unlike other exoplanets, it is bright in the optical and nondetected in the infrared, and its orbit appears to cross the debris ring around the star withou...

    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.1912506117

    authors： Gáspár A,Rieke GH

    更新日期：2020-05-05 00:00:00

  • MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production.

    abstract：:MicroRNAs (miRNAs) are small, 18-22 nt long, noncoding RNAs that act as potent negative gene regulators in a variety of physiological and pathological processes. To repress gene expression, miRNAs are packaged into RNA-induced silencing complexes (RISCs) that target mRNAs for degradation and/or translational repressio...

    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.1408037111

    authors： Chen AK,Sengupta P,Waki K,Van Engelenburg SB,Ochiya T,Ablan SD,Freed EO,Lippincott-Schwartz J

    更新日期：2014-07-01 00:00:00

  • Intrinsic expression of viperin regulates thermogenesis in adipose tissues.

    abstract：:Viperin is an interferon (IFN)-inducible multifunctional protein. Recent evidence from high-throughput analyses indicates that most IFN-inducible proteins, including viperin, are intrinsically expressed in specific tissues; however, the respective intrinsic functions are unknown. Here we show that the intrinsic expres...

    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.1904480116

    authors： Eom J,Kim JJ,Yoon SG,Jeong H,Son S,Lee JB,Yoo J,Seo HJ,Cho Y,Kim KS,Choi KM,Kim IY,Lee HY,Nam KT,Cresswell P,Seong JK,Seo JY

    更新日期：2019-08-27 00:00:00

  • Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene.

    abstract：:Several mouse models have already proved valuable for investigating hypertrophic responses to cardiac stress. Here, we characterize one caused by a well defined single copy transgene, RenTgMK, that genetically clamps plasma renin and thence angiotensin II at high levels. All of the transgenic males develop concentric ...

    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.0307333101

    authors： Caron KM,James LR,Kim HS,Knowles J,Uhlir R,Mao L,Hagaman JR,Cascio W,Rockman H,Smithies O

    更新日期：2004-03-02 00:00:00

  • TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domains.

    abstract：:Previous work has established stargazin and its related family of transmembrane AMPA receptor regulatory proteins (TARPs) as auxiliary subunits of AMPA receptors (AMPARs) that control synaptic strength both by targeting AMPARs to synapses through an intracellular PDZ-binding motif and by modulating their gating throug...

    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.0905570106

    authors： Milstein AD,Nicoll RA

    更新日期：2009-07-07 00:00:00