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Search results 301 to 400 out of 427 for Irs2

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Type Details Score
Publication
18202124 | J:136031
First Author: Lee S
Year: 2008
Journal: Endocrinology
Title: Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling.
Volume: 149
Issue: 5
Pages: 2451-8
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Publication
11147812 | J:137434
First Author: Miranda C
Year: 2001
Journal: J Cell Physiol
Title: IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1.
Volume: 186
Issue: 1
Pages: 35-46
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Publication
15169905 | J:91027
First Author: Ueki K
Year: 2004
Journal: Mol Cell Biol
Title: Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
Volume: 24
Issue: 12
Pages: 5434-46
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Publication
10471495 | J:57319
First Author: Withers DJ
Year: 1999
Journal: Nat Genet
Title: Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling.
Volume: 23
Issue: 1
Pages: 32-40
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Publication
28798046 | J:249957
 
First Author: Piwecka M
Year: 2017
Journal: Science
Title: Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.
Volume: 357
Issue: 6357
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Publication
18256806 | J:137955
First Author: Tsuneki H
Year: 2008
Journal: Diabetologia
Title: Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice.
Volume: 51
Issue: 4
Pages: 657-67
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Publication
9624169 | J:48179
First Author: Yamauchi T
Year: 1998
Journal: J Biol Chem
Title: Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase.
Volume: 273
Issue: 25
Pages: 15719-26
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Publication
19007875 | J:146582
First Author: Swindell WR
Year: 2009
Journal: Exp Gerontol
Title: Accelerated failure time models provide a useful statistical framework for aging research.
Volume: 44
Issue: 3
Pages: 190-200
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Publication
12810823 | J:94547
First Author: Sehayek E
Year: 2003
Journal: J Lipid Res
Title: Loci controlling plasma non-HDL and HDL cholesterol levels in a C57BL /6J x CASA /Rk intercross.
Volume: 44
Issue: 9
Pages: 1744-50
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Publication
17662267 | J:124667
First Author: Heckman BM
Year: 2007
Journal: Dev Biol
Title: Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development.
Volume: 309
Issue: 1
Pages: 137-49
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Publication
15587270 | J:94589
First Author: Lamotte L
Year: 2004
Journal: Transgenic Res
Title: Knock-in of diphteria toxin A chain gene at Ins2 locus: effects on islet development and localization of Ins2 expression in the brain.
Volume: 13
Issue: 5
Pages: 463-73
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Publication
21293061 | J:171817
First Author: Huang G
Year: 2011
Journal: J Clin Invest
Title: α3(V) collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues.
Volume: 121
Issue: 2
Pages: 769-83
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Publication
16565260 | J:109514
First Author: Vats KR
Year: 2006
Journal: J Am Soc Nephrol
Title: A locus for renal malformations including vesico-ureteric reflux on chromosome 13q33-34.
Volume: 17
Issue: 4
Pages: 1158-67
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Publication
11897712 | J:106827
First Author: Duvillié B
Year: 2002
Journal: Endocrinology
Title: Increased islet cell proliferation, decreased apoptosis, and greater vascularization leading to beta-cell hyperplasia in mutant mice lacking insulin.
Volume: 143
Issue: 4
Pages: 1530-7
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Publication
24874427 | J:247084
First Author: Dharaneeswaran H
Year: 2014
Journal: Circ Res
Title: FOXO1-mediated activation of Akt plays a critical role in vascular homeostasis.
Volume: 115
Issue: 2
Pages: 238-251
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Publication
33184218 | J:303230
First Author: Ray AT
Year: 2020
Journal: Genes Dev
Title: FGF signaling regulates development by processes beyond canonical pathways.
Volume: 34
Issue: 23-24
Pages: 1735-1752
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Publication
30858352 | J:276962
First Author: Kon N
Year: 2019
Journal: Cell Death Dis
Title: Loss of SET reveals both the p53-dependent and the p53-independent functions in vivo.
Volume: 10
Issue: 3
Pages: 237
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Publication
21238928 | J:168571
First Author: Zou J
Year: 2011
Journal: Dev Cell
Title: Rheb1 is required for mTORC1 and myelination in postnatal brain development.
Volume: 20
Issue: 1
Pages: 97-108
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Publication
29728617 | J:262992
First Author: Zhuang L
Year: 2018
Journal: Nat Commun
Title: Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function.
Volume: 9
Issue: 1
Pages: 1796
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Publication
35377412 | J:333870
First Author: Jazwiec PA
Year: 2022
Journal: Biol Reprod
Title: Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism†.
Volume: 107
Issue: 2
Pages: 574-589
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Publication
33505018 | J:305792
First Author: Ansarullah
Year: 2021
Journal: Nature
Title: Inceptor counteracts insulin signalling in β-cells to control glycaemia.
Volume: 590
Issue: 7845
Pages: 326-331
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Publication
20111592 | J:223633
First Author: Sanchez-Calderon H
Year: 2010
Journal: PLoS One
Title: RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.
Volume: 5
Issue: 1
Pages: e8699
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Publication
23907538 | J:203690
First Author: Martinez-Lopez N
Year: 2013
Journal: EMBO Rep
Title: Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development.
Volume: 14
Issue: 9
Pages: 795-803
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Publication
32290105 | J:282558
 
First Author: Collin GB
Year: 2020
Journal: Cells
Title: Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss.
Volume: 9
Issue: 4
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Publication
- | J:265051
     
First Author: MGI and IMPC
Year: 2018
Journal: Database Release
Title: MGI Load of Endonuclease-Mediated Alleles (CRISPR) from the International Mouse Phenotyping Consortium (IMPC)
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Publication
- | J:342605
       
First Author: GOA curators
Year: 2016
Title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
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Publication
- | J:155856
       
First Author: Mouse Genome Informatics Scientific Curators
Year: 2010
Title: Rat to Mouse ISO GO annotation transfer
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Publication
16141072 | J:99680
First Author: Carninci P
Year: 2005
Journal: Science
Title: The transcriptional landscape of the mammalian genome.
Volume: 309
Issue: 5740
Pages: 1559-63
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Publication
- | J:164563
       
First Author: Mouse Genome Informatics Scientific Curators
Year: 2010
Title: Human to Mouse ISO GO annotation transfer
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Publication
21267068 | J:153498
First Author: Diez-Roux G
Year: 2011
Journal: PLoS Biol
Title: A high-resolution anatomical atlas of the transcriptome in the mouse embryo.
Volume: 9
Issue: 1
Pages: e1000582
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Publication
- | J:157972
     
First Author: Mouse Genome Informatics Scientific Curators
Year: 2010
Journal: Database Download
Title: Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Genome U74 Array Platform (A, B, C v2).
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Publication
- | J:57747
     
First Author: MGI Genome Annotation Group and UniGene Staff
Year: 2015
Journal: Database Download
Title: MGI-UniGene Interconnection Effort
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Publication
- | J:75000
       
First Author: Mouse Genome Informatics Scientific Curators
Year: 2002
Title: Mouse Genome Informatics Computational Sequence to Gene Associations
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Publication
- | J:161428
       
First Author: Marc Feuermann, Huaiyu Mi, Pascale Gaudet, Dustin Ebert, Anushya Muruganujan, Paul Thomas
Year: 2010
Title: Annotation inferences using phylogenetic trees
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Publication
- | J:53168
     
First Author: Bairoch A
Year: 1999
Journal: Database Release
Title: SWISS-PROT Annotated protein sequence database
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Publication
- | J:91388
       
First Author: Mouse Genome Informatics Scientific Curators
Year: 2005
Title: Obtaining and Loading Genome Assembly Coordinates from Ensembl Annotations
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Publication
- | J:90438
       
First Author: Mouse Genome Informatics Scientific Curators
Year: 2005
Title: Obtaining and loading genome assembly coordinates from NCBI annotations
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Publication
- | J:155721
     
First Author: Mouse Genome Informatics (MGI) and The National Center for Biotechnology Information (NCBI)
Year: 2010
Journal: Database Download
Title: Consensus CDS project
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Publication
- | J:155221
     
First Author: Mouse Genome Informatics
Year: 2010
Journal: Database Release
Title: Protein Ontology Association Load.
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Publication
- | J:63103
     
First Author: Mouse Genome Database and National Center for Biotechnology Information
Year: 2000
Journal: Database Release
Title: Entrez Gene Load
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Publication
- | J:262123
     
First Author: Allen Institute for Brain Science
Year: 2004
Journal: Allen Institute
Title: Allen Brain Atlas: mouse riboprobes
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Publication
- | J:144086
     
First Author: Mouse Genome Informatics Scientific Curators
Year: 2009
Journal: Database Download
Title: Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Gene 1.0 ST Array Platform
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Publication
- | J:85324
     
First Author: Mouse Genome Informatics Group
Year: 2003
Journal: Database Procedure
Title: Automatic Encodes (AutoE) Reference
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Publication
- | J:144087
     
First Author: Mouse Genome Informatics Scientific Curators
Year: 2009
Journal: Database Download
Title: Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Genome 430 2.0 Array Platform
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HT Experiment
E-GEOD-43620 | Effects of sodium tungstate administration in Irs2 -/- mice
Series Id: GSE43620
Experiment Type: transcription profiling by array
Study Type: WT vs. Mutant
Source: ArrayExpress
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HT Experiment
E-MEXP-1649 | Transcription profiling of mouse liver cells with liver specific deletion of Irs1 and/or Irs2 and Foxo1during fasting and feeding
 
Experiment Type: transcription profiling by array
Study Type: WT vs. Mutant
Source: ArrayExpress
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Publication
27152363 | J:293590
 
First Author: Kuznetsova A
Year: 2016
Journal: JCI Insight
Title: Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice.
Volume: 1
Issue: 3
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HT Experiment
GSE151068 | Repression of Irs2 by let-7 miRNAs is essential for the homeostasis of the telencephalic neuroepithelium [RNA-seq]
 
Experiment Type: RNA-Seq
Study Type: WT vs. Mutant
Source: GEO
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HT Experiment
GSE151148 | Repression of Irs2 by let-7 miRNAs is essential for the homeostasis of the telencephalic neuroepithelium [miRNA-seq]
 
Experiment Type: RNA-Seq
Study Type: WT vs. Mutant
Source: GEO
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Allele
Gt(ROSA)26Sor<tm3(CAG-Irs2)Mschu> | MGI:6861841
Name: gene trap ROSA 26, Philippe Soriano; targeted mutation 3, Markus Schubert
Allele Type: Targeted
Attribute String: Conditional ready, Epitope tag, Inserted expressed sequence, Reporter
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Allele
Tg(Ins2-Irs2)13Mfw | MGI:3510672
Name: transgene insertion 13, Morris F White
Allele Type: Transgenic
Attribute String: Inserted expressed sequence
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Allele
Irs2<M1Btlr> | MGI:6268726
Name: insulin receptor substrate 2; mutaiton 1, Bruce Beutler
Allele Type: Chemically induced (ENU)
Attribute String: Not Specified
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Strain
MGI:6268727 | C57BL/6J-Irs2<M1Btlr>
Attribute String: mutant strain, chemically induced mutation, coisogenic
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Genotype
Genotype
Symbol: Irs2/Irs2
Background: C57BL/6J-Irs2
Zygosity: hm
Has Mutant Allele: true
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Genotype
Genotype
Symbol: Tg(Ins2-Irs2)13Mfw/?
Background: involves: C57BL/6
Zygosity: ot
Has Mutant Allele: true
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Publication
23160735 | J:318815
First Author: Zemva J
Year: 2013
Journal: Age (Dordr)
Title: Neuronal overexpression of insulin receptor substrate 2 leads to increased fat mass, insulin resistance, and glucose intolerance during aging.
Volume: 35
Issue: 5
Pages: 1881-97
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Genotype
Genotype
Symbol: Irs2/Irs2 Tg(Ins2-Irs2)13Mfw/?
Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Zygosity: cx
Has Mutant Allele: true
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Genotype
Genotype
Symbol: Irs2/Irs2 Tg(Ins2-cre)25Mgn/? Tg(Ins2-Irs2)13Mfw/?
Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Zygosity: cn
Has Mutant Allele: true
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Publication
16098827 | J:129837
First Author: Ren D
Year: 2005
Journal: Cell Metab
Title: Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice.
Volume: 2
Issue: 2
Pages: 95-104
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Publication
15554902 | J:117521
First Author: Mora A
Year: 2005
Journal: Biochem J
Title: Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure.
Volume: 385
Issue: Pt 3
Pages: 639-48
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Publication
18362393 | J:138463
First Author: Su Z
Year: 2008
Journal: J Lipid Res
Title: Candidate genes for plasma triglyceride, FFA, and glucose revealed from an intercross between inbred mouse strains NZB/B1NJ and NZW/LacJ.
Volume: 49
Issue: 7
Pages: 1500-10
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Publication
18029451 | J:128497
First Author: Xie T
Year: 2007
Journal: Proc Natl Acad Sci U S A
Title: Beta cell-specific deficiency of the stimulatory G protein alpha-subunit Gsalpha leads to reduced beta cell mass and insulin-deficient diabetes.
Volume: 104
Issue: 49
Pages: 19601-6
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Publication
35657825 | J:328526
First Author: Lynch EC
Year: 2022
Journal: PLoS One
Title: Disrupting Osr1 expression promoted hepatic steatosis and inflammation induced by high-fat diet in the mouse model.
Volume: 17
Issue: 6
Pages: e0268344
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Publication
18349318 | J:136083
First Author: Sathyanarayana P
Year: 2008
Journal: Blood
Title: EPO receptor circuits for primary erythroblast survival.
Volume: 111
Issue: 11
Pages: 5390-9
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Publication
22128176 | J:181385
First Author: Jurczak MJ
Year: 2012
Journal: J Biol Chem
Title: Dissociation of inositol-requiring enzyme (IRE1α)-mediated c-Jun N-terminal kinase activation from hepatic insulin resistance in conditional X-box-binding protein-1 (XBP1) knock-out mice.
Volume: 287
Issue: 4
Pages: 2558-67
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Publication
31908399 | J:285493
 
First Author: Minogue PJ
Year: 2019
Journal: Mol Vis
Title: CHOP is dispensable for lens transparency in wild-type and connexin50 mutant mice.
Volume: 25
Pages: 535-545
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Publication
27317663 | J:236170
First Author: Berthoud VM
Year: 2016
Journal: J Biol Chem
Title: The Cataract-linked Mutant Connexin50D47A Causes Endoplasmic Reticulum Stress in Mouse Lenses.
Volume: 291
Issue: 34
Pages: 17569-78
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Publication
24204824 | J:209176
First Author: Lau SM
Year: 2013
Journal: PLoS One
Title: Beta-cell ARNT is required for normal glucose tolerance in murine pregnancy.
Volume: 8
Issue: 10
Pages: e77419
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Publication
17551001 | J:123371
First Author: Li L
Year: 2007
Journal: Am J Physiol Endocrinol Metab
Title: LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling.
Volume: 293
Issue: 2
Pages: E587-94
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Publication
24037093 | J:202021
First Author: Taniguchi CM
Year: 2013
Journal: Nat Med
Title: Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes.
Volume: 19
Issue: 10
Pages: 1325-30
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Publication
33297755 | J:318576
First Author: Sun J
Year: 2021
Journal: Arterioscler Thromb Vasc Biol
Title: Endothelial TFEB (Transcription Factor EB) Improves Glucose Tolerance via Upregulation of IRS (Insulin Receptor Substrate) 1 and IRS2.
Volume: 41
Issue: 2
Pages: 783-795
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Publication
15314154 | J:92794
First Author: Duan C
Year: 2004
Journal: Mol Cell Biol
Title: Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance.
Volume: 24
Issue: 17
Pages: 7435-43
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Publication
15181014 | J:121205
First Author: Shi H
Year: 2004
Journal: J Biol Chem
Title: Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling.
Volume: 279
Issue: 33
Pages: 34733-40
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Publication
23349480 | J:208573
First Author: Tsuchiya K
Year: 2013
Journal: Diabetes
Title: Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance.
Volume: 62
Issue: 5
Pages: 1478-89
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Publication
24435134 | J:210098
 
First Author: Ong QR
Year: 2014
Journal: Sci Rep
Title: Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.
Volume: 4
Pages: 3754
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Publication
30685084 | J:291078
First Author: Zhou Y
Year: 2019
Journal: Biochem Biophys Res Commun
Title: Iron regulatory protein 2 deficiency may correlate with insulin resistance.
Volume: 510
Issue: 2
Pages: 191-197
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Publication
22854958 | J:190396
First Author: Huang L
Year: 2012
Journal: J Biol Chem
Title: Znt7-null mice are more susceptible to diet-induced glucose intolerance and insulin resistance.
Volume: 287
Issue: 40
Pages: 33883-96
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Publication
22076926 | J:191388
First Author: Wu S
Year: 2012
Journal: Diabetes
Title: Reproductive tissues maintain insulin sensitivity in diet-induced obesity.
Volume: 61
Issue: 1
Pages: 114-23
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Publication
10995442 | J:68751
First Author: Sachs M
Year: 2000
Journal: J Cell Biol
Title: Essential role of Gab1 for signaling by the c-Met receptor in vivo.
Volume: 150
Issue: 6
Pages: 1375-84
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Publication
20411234 | J:162167
First Author: Fritsche L
Year: 2010
Journal: Diabetologia
Title: IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise.
Volume: 53
Issue: 8
Pages: 1732-42
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Publication
23901139 | J:259996
First Author: Ersoy BA
Year: 2013
Journal: Sci Signal
Title: Phosphatidylcholine transfer protein interacts with thioesterase superfamily member 2 to attenuate insulin signaling.
Volume: 6
Issue: 286
Pages: ra64
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Publication
14978080 | J:88239
First Author: Kelly-Welch AE
Year: 2004
Journal: J Immunol
Title: Transgenic expression of insulin receptor substrate 2 in murine B cells alters the cell density-dependence of IgE production in vitro and enhances IgE production in vivo.
Volume: 172
Issue: 5
Pages: 2803-10
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Publication
18682608 | J:143133
First Author: Ishikawa M
Year: 2008
Journal: J Lipid Res
Title: Cholesterol accumulation and diabetes in pancreatic beta-cell-specific SREBP-2 transgenic mice: a new model for lipotoxicity.
Volume: 49
Issue: 12
Pages: 2524-34
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Publication
29483197 | J:263703
First Author: Torii S
Year: 2018
Journal: J Biol Chem
Title: The pseudophosphatase phogrin enables glucose-stimulated insulin signaling in pancreatic β cells.
Volume: 293
Issue: 16
Pages: 5920-5933
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Publication
28122332 | J:276628
First Author: Tan Y
Year: 2017
Journal: Oncotarget
Title: The homeoprotein Dlx5 drives murine T-cell lymphomagenesis by directly transactivating Notch and upregulating Akt signaling.
Volume: 8
Issue: 9
Pages: 14941-14956
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Publication
33408127 | J:306294
First Author: Liao W
Year: 2021
Journal: Diabetes
Title: Heme Oxygenase-1 Regulates Ferrous Iron and Foxo1 in Control of Hepatic Gluconeogenesis.
Volume: 70
Issue: 3
Pages: 696-709
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Publication
32534258 | J:330764
 
First Author: Riopel M
Year: 2020
Journal: Mol Metab
Title: Inhibition of prolyl hydroxylases increases hepatic insulin and decreases glucagon sensitivity by an HIF-2α-dependent mechanism.
Volume: 41
Pages: 101039
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Publication
27765041 | J:316548
First Author: Farabaugh SM
Year: 2016
Journal: Cell Commun Signal
Title: Lack of interaction between ErbB2 and insulin receptor substrate signaling in breast cancer.
Volume: 14
Issue: 1
Pages: 25
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Publication
36217412 | J:330009
 
First Author: Zhang YC
Year: 2022
Journal: Oxid Med Cell Longev
Title: KCNH6 Enhanced Hepatic Glucose Metabolism through Mitochondrial Ca2+ Regulation and Oxidative Stress Inhibition.
Volume: 2022
Pages: 3739556
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Publication
36868363 | J:335047
 
First Author: Grover L
Year: 2023
Journal: Behav Brain Res
Title: Diet, sex, and genetic predisposition to obesity and type 2 diabetes modulate motor and anxiety-related behaviors in mice, and alter cerebellar gene expression.
Volume: 445
Pages: 114376
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Publication
24887203 | J:217927
First Author: Pedrós I
Year: 2014
Journal: Biochim Biophys Acta
Title: Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse model of Alzheimer's disease.
Volume: 1842
Issue: 9
Pages: 1556-66
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Publication
26812158 | J:233901
First Author: Rogers NH
Year: 2016
Journal: Endocrinology
Title: Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin.
Volume: 157
Issue: 4
Pages: 1430-42
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Publication
24503961 | J:212968
First Author: Rodríguez-de la Rosa L
Year: 2014
Journal: PLoS One
Title: Treatment with N- and C-terminal peptides of parathyroid hormone-related protein partly compensate the skeletal abnormalities in IGF-I deficient mice.
Volume: 9
Issue: 2
Pages: e87536
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Publication
24989997 | J:218130
First Author: Chen YC
Year: 2014
Journal: Diabetologia
Title: Mig6 haploinsufficiency protects mice against streptozotocin-induced diabetes.
Volume: 57
Issue: 10
Pages: 2066-75
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Publication
20821187 | J:164577
First Author: Liu Y
Year: 2010
Journal: Diabetologia
Title: Conditional ablation of Gsk-3β in islet beta cells results in expanded mass and resistance to fat feeding-induced diabetes in mice.
Volume: 53
Issue: 12
Pages: 2600-10
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Publication
23359250 | J:320787
First Author: Rector RS
Year: 2013
Journal: Hepatology
Title: Selective hepatic insulin resistance in a murine model heterozygous for a mitochondrial trifunctional protein defect.
Volume: 57
Issue: 6
Pages: 2213-23
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Publication
18045056 | -
First Author: Uckun FM
Year: 2007
Journal: Anticancer Agents Med Chem
Title: Targeting JAK3 tyrosine kinase-linked signal transduction pathways with rationally-designed inhibitors.
Volume: 7
Issue: 6
Pages: 612-23
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Protein Domain
IPR020775 | Tyr_kinase_non-rcpt_Jak3
Type: Family
Description: Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups []:Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis []. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction []. Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [].Janus kinases (JAKs) are tyrosine kinases that function in membrane-proximal signalling events initiated by a variety of extracellular factors binding to cell surface receptors []. Many type I and II cytokine receptors lack a protein tyrosine kinase domain and rely on JAKs to initiate the cytoplasmic signal transduction cascade. Ligand binding induces oligomerisation of the receptors, which then activates the cytoplasmic receptor-associated JAKs. These subsequently phosphorylate tyrosine residues along the receptor chains with which they are associated. The phosphotyrosine residues are a target for a variety of SH2 domain-containing transducer proteins. Amongst these are the signal transducers and activators of transcription (STAT) proteins, which, after binding to the receptor chains, are phosphorylated by the JAK proteins. Phosphorylation enables the STAT proteins to dimerise and translocate into the nucleus, where they alter the expression of cytokine-regulated genes. This system is known as the JAK-STAT pathway.Four mammalian JAK family members have been identified: JAK1, JAK2, JAK3, and TYK2. They are relatively large kinases of approximately 1150 amino acids, with molecular weights of ~120-130kDa. Their amino acid sequences are characterised by the presence of 7 highly conserved domains, termed JAK homology (JH) domains. The C-terminal domain (JH1) is responsible for the tyrosine kinase function. The next domain in the sequence (JH2) is known as the tyrosine kinase-like domain, as its sequence shows high similarity to functional kinases but does not possess any catalytic activity. Although the function of this domain is not well established, there is some evidence for a regulatory role on the JH1 domain, thus modulating catalytic activity. The N-terminal portion of the JAKs (spanning JH7 to JH3) is important for receptor association and non-catalytic activity, and consists of JH3-JH4, which is homologous to the SH2 domain, and lastly JH5-JH7, which is a FERM domain.This represents the non-receptor tyrosine kinase JAK3, which is involved in the interleukin-2 and interleukin-4 signalling pathway. Jak3 phosphorylates STAT6, IRS1, IRS2 and PI3K [].
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Publication
9096349 | -
First Author: Conway G
Year: 1997
Journal: Proc Natl Acad Sci U S A
Title: Jak1 kinase is required for cell migrations and anterior specification in zebrafish embryos.
Volume: 94
Issue: 7
Pages: 3082-7
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Publication
19660986 | -
First Author: Lai X
Year: 2009
Journal: Comput Biol Chem
Title: A multi-level model accounting for the effects of JAK2-STAT5 signal modulation in erythropoiesis.
Volume: 33
Issue: 4
Pages: 312-24
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