Ser73
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Home > Phosphorylation Site Page: > Ser73  -  Jun (mouse)

Site Information
VGLLKLAsPELERLI   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447943

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 40 ) , flow cytometry ( 4 ) , immunoprecipitation ( 3 ) , mass spectrometry ( 1 , 5 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 ) , mutation of modification site ( 26 , 27 , 31 , 32 , 35 , 41 , 42 ) , phospho-antibody ( 3 , 4 , 6 , 22 , 25 , 26 , 27 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ) , phosphopeptide mapping ( 40 ) , western blotting ( 3 , 4 , 6 , 22 , 25 , 26 , 27 , 29 , 31 , 33 , 34 , 35 , 36 , 39 , 40 , 41 , 42 )
Disease tissue studied:
bladder cancer ( 4 ) , leukemia ( 14 ) , acute myelogenous leukemia ( 14 ) , melanoma skin cancer ( 24 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 10 ) , 'brain, striatum' ( 36 ) , 'neuron, cerebellar granule'-brain ( 29 ) , 'neuron, sympathetic' ( 31 ) , 293 (epithelial) ( 3 , 25 , 40 ) , 32Dcl3 (myeloid) [FLT3 (mouse), transfection, chimera with human FLT3-ITD mutant (corresponding to wild type P36888 ( 21 ) , 32Dcl3 (myeloid) ( 21 ) , 3T3 (fibroblast) [INSR (human)] ( 40 ) , 3T3 (fibroblast) ( 27 , 39 , 41 ) , BaF3 ('B lymphocyte, precursor') [JAK3 (human), transfection] ( 1 ) , blood ( 14 ) , brain ( 15 , 18 ) , FL5.12 (lymphoid) ( 33 ) , heart ( 11 ) , HEK293T (epithelial) ( 27 , 29 ) , HeLa (cervical) ( 42 ) , HL-1 (myocyte) [Akt1 (mouse), knockdown, stable lentiviral expression of Akt1 shRNA] ( 8 ) , HL-1 (myocyte) [Akt2 (mouse), knockdown, stable lentiviral expression of Akt2 shRNA] ( 8 ) , HL-1 (myocyte) ( 8 ) , kidney ( 18 ) , liver ( 13 , 22 ) , liver [leptin (mouse), homozygous knockout] ( 13 ) , lung ( 18 ) , macrophage-bone marrow ( 19 ) , macrophage-bone marrow [DUSP1 (mouse), homozygous knockout] ( 19 ) , MC3T3-E1 (preosteoblast) ( 5 ) , MEF (fibroblast) ( 3 , 4 , 12 , 17 , 26 , 32 , 34 , 35 ) , MEF (fibroblast) [IGF1R (mouse)] ( 30 , 37 ) , MEF (fibroblast) [JNK1 (mouse), transfection] ( 25 ) , MEF (fibroblast) [Jun (mouse), homozygous knockout] ( 41 ) , MEF (fibroblast) [p53 (mouse), homozygous knockout] ( 16 ) , MEF (fibroblast) [Raptor (mouse), knockdown] ( 12 ) , MEF (fibroblast) [RICTOR (mouse), knockdown] ( 12 ) , MEF (fibroblast) [TSC2 (mouse), homozygous knockout] ( 17 ) , mpkCCD (renal) ( 20 ) , MRC5 (fibroblast) ( 26 ) , NMuMG (epithelial) ( 6 ) , pancreas ( 18 ) , Rat1 (fibroblast) ( 39 ) , RAW 264 (macrophage) ( 34 ) , RAW 264.7 (macrophage) ( 7 ) , RAW 267.4 (macrophage) ( 23 ) , skin [mGluR1 (mouse), transgenic, TG mutant mice] ( 24 ) , spleen ( 18 ) , synoviocyte ( 38 ) , T24 (bladder cell) ( 4 ) , UMUC3 (bladder cell) ( 4 )

Upstream Regulation
Regulatory protein:
AMD1 (mouse) ( 39 ) , basonuclin 1 (human) ( 6 ) , CTNNB1 (mouse) ( 25 ) , Fos (mouse) ( 41 ) , HRas (mouse) ( 40 ) , IGF1R (mouse) ( 33 ) , JNK1 (human) ( 25 ) , JNK1 (mouse) ( 22 , 39 ) , JNK2 (mouse) ( 22 ) , MKK4 (mouse) ( 39 ) , NFkB-p100 (mouse) ( 3 , 4 ) , PXN (mouse) ( 28 ) , RALB (mouse) ( 40 ) , RALBP1 (mouse) ( 40 ) , RALGDS (human) ( 40 ) , Raptor (mouse) ( 12 ) , RLF (mouse) ( 40 ) , RRas (mouse) ( 41 ) , Src (mouse) ( 41 )
Putative in vivo kinases:
ERK1 (mouse) ( 34 ) , JNK1 (mouse) ( 34 )
Kinases, in vitro:
JNK1 (mouse) ( 34 )
Treatments:
anisomycin ( 34 ) , ConA ( 22 ) , EGF ( 28 , 34 , 40 ) , IFN-gamma ( 23 ) , IGF-1 ( 33 ) , IL-1a ( 26 ) , IL-1b ( 38 ) , insulin ( 10 , 40 ) , kainic_acid ( 29 ) , KN-62 ( 29 ) , lithium ( 29 ) , LPS ( 19 , 34 ) , LY294002 ( 40 ) , metamfetamine ( 36 ) , NGF_withdrawal ( 31 ) , nimodipine ( 29 ) , PD184352 ( 34 ) , PD98059 ( 38 , 40 ) , phorbol_ester ( 28 , 30 , 34 ) , PP1 ( 40 ) , rottlerin ( 29 ) , SB203580 ( 34 , 38 ) , siRNA ( 28 ) , SP600125 ( 35 , 38 ) , TGF-beta ( 6 ) , TNF ( 34 ) , U0126 ( 3 ) , UV ( 37 )

Downstream Regulation
Effects of modification on Jun:
acetylation ( 26 ) , activity, induced ( 27 ) , molecular association, regulation ( 26 ) , sumoylation ( 42 )
Effects of modification on biological processes:
apoptosis, induced ( 31 , 32 ) , cell growth, altered ( 41 ) , cell motility, altered ( 35 ) , transcription, altered ( 27 , 31 ) , transcription, induced ( 26 , 42 )
Induce interaction with:
DNA ( 26 ) , NFkB-p65 (human) ( 26 )
Inhibit interaction with:
HDAC3 (human) ( 26 )

Disease / Diagnostics Relevance
Relevant diseases:
non-melanoma skin cancer ( 41 )

References 

1

Degryse S, et al. (2017) Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia. Leukemia
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2

Sacco F, et al. (2016) Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nat Commun 7, 13250
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3

Wang Y, et al. (2016) Tumor-suppressor NFκB2 p100 interacts with ERK2 and stabilizes PTEN mRNA via inhibition of miR-494. Oncogene 35, 4080-90
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4

Xu J, et al. (2016) Inhibition of PHLPP2/cyclin D1 protein translation contributes to the tumor suppressive effect of NFκB2 (p100). Oncotarget 7, 34112-30
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5

Williams GR, et al. (2016) Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics. Methods 92, 36-50
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6

Feuerborn A, et al. (2015) Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity. Oncogene 34, 1185-95
24662832   Curated Info

7

Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44
25367039   Curated Info

8

Reinartz M, Raupach A, Kaisers W, Gödecke A (2014) AKT1 and AKT2 induce distinct phosphorylation patterns in HL-1 cardiac myocytes. J Proteome Res 13, 4232-45
25162660   Curated Info

9

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
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10

Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20
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11

Lundby A, et al. (2013) In vivo phosphoproteomics analysis reveals the cardiac targets of β-adrenergic receptor signaling. Sci Signal 6, rs11
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12

Robitaille AM, et al. (2013) Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science 339, 1320-3
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13

Grimsrud PA, et al. (2012) A quantitative map of the liver mitochondrial phosphoproteome reveals posttranslational control of ketogenesis. Cell Metab 16, 672-83
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14

Trost M, et al. (2012) Posttranslational regulation of self-renewal capacity: insights from proteome and phosphoproteome analyses of stem cell leukemia. Blood 120, e17-27
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15

Goswami T, et al. (2012) Comparative phosphoproteomic analysis of neonatal and adult murine brain. Proteomics 12, 2185-9
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16

Hsu PP, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-22
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17

Yu Y, et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-6
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18

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
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19

Weintz G, et al. (2010) The phosphoproteome of toll-like receptor-activated macrophages. Mol Syst Biol 6, 371
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20

Rinschen MM, et al. (2010) Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells. Proc Natl Acad Sci U S A 107, 3882-7
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21

Choudhary C, et al. (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326-39
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22

Das M, et al. (2009) Induction of hepatitis by JNK-mediated expression of TNF-alpha. Cell 136, 249-60
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23

Trost M, et al. (2009) The phagosomal proteome in interferon-gamma-activated macrophages. Immunity 30, 143-54
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24

Zanivan S, et al. (2008) Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry. J Proteome Res 7, 5314-26
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25

Hu D, et al. (2008) c-Jun N-terminal kinase 1 interacts with and negatively regulates Wnt/beta-catenin signaling through GSK3beta pathway. Carcinogenesis 29, 2317-24
18952597   Curated Info

26

Wolter S, et al. (2008) c-Jun controls histone modifications, NF-kappaB recruitment, and RNA polymerase II function to activate the ccl2 gene. Mol Cell Biol 28, 4407-23
18443042   Curated Info

27

Tsuchiya A, Tashiro E, Yoshida M, Imoto M (2007) Involvement of protein phosphatase 2A nuclear accumulation and subsequent inactivation of activator protein-1 in leptomycin B-inhibited cyclin D1 expression. Oncogene 26, 1522-32
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28

Tatsumi Y, et al. (2006) Involvement of the paxillin pathway in JB6 Cl41 cell transformation. Cancer Res 66, 5968-74
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29

Tomomura M, Furuichi T (2005) Apoptosis-associated tyrosine kinase (AATYK) has differential Ca2+-dependent phosphorylation states in response to survival and apoptotic conditions in cerebellar granule cells. J Biol Chem 280, 35157-63
16100393   Curated Info

30

Müssig K, et al. (2005) Shp2 is required for protein kinase C-dependent phosphorylation of serine 307 in insulin receptor substrate-1. J Biol Chem 280, 32693-9
16055440   Curated Info

31

Besirli CG, Wagner EF, Johnson EM (2005) The limited role of NH2-terminal c-Jun phosphorylation in neuronal apoptosis: identification of the nuclear pore complex as a potential target of the JNK pathway. J Cell Biol 170, 401-11
16061693   Curated Info

32

Cuadrado A, et al. (2004) JNK activation is critical for Aplidin-induced apoptosis. Oncogene 23, 4673-80
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33

Leahy M, Lyons A, Krause D, O'Connor R (2004) Impaired Shc, Ras, and MAPK activation but normal Akt activation in FL5.12 cells expressing an insulin-like growth factor I receptor mutated at tyrosines 1250 and 1251. J Biol Chem 279, 18306-13
14963047   Curated Info

34

Morton S, Davis RJ, McLaren A, Cohen P (2003) A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. EMBO J 22, 3876-86
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35

Javelaud D, et al. (2003) Disruption of basal JNK activity differentially affects key fibroblast functions important for wound healing. J Biol Chem 278, 24624-8
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36

Jayanthi S, McCoy MT, Ladenheim B, Cadet JL (2002) Methamphetamine causes coordinate regulation of Src, Cas, Crk, and the Jun N-terminal kinase-Jun pathway. Mol Pharmacol 61, 1124-31
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37

She QB, Ma WY, Dong Z (2002) Role of MAP kinases in UVB-induced phosphorylation of p53 at serine 20. Oncogene 21, 1580-9
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38

Han Z, et al. (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 108, 73-81
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39

Paasinen-Sohns A, et al. (2000) c-Jun activation-dependent tumorigenic transformation induced paradoxically by overexpression or block of S-adenosylmethionine decarboxylase. J Cell Biol 151, 801-10
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40

de Ruiter ND, et al. (2000) Ras-dependent regulation of c-Jun phosphorylation is mediated by the Ral guanine nucleotide exchange factor-Ral pathway. Mol Cell Biol 20, 8480-8
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41

Behrens A, Jochum W, Sibilia M, Wagner EF (2000) Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene 19, 2657-63
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42

Muller S, et al. (2000) c-Jun and p53 activity is modulated by SUMO-1 modification. J Biol Chem 275, 13321-9
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