Ser63
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Home > Phosphorylation Site Page: > Ser63  -  Jun (mouse)

Site Information
kNsDLLtsPDVGLLK   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447686

In vivo Characterization
Methods used to characterize site in vivo:
[32P] ATP in vitro ( 22 ) , [32P] bio-synthetic labeling ( 39 ) , immunoprecipitation ( 22 ) , mass spectrometry ( 4 , 6 , 8 , 9 , 11 , 12 , 14 , 17 ) , mutation of modification site ( 18 , 20 , 23 , 28 , 31 , 33 , 36 , 40 , 41 ) , phospho-antibody ( 1 , 2 , 3 , 7 , 10 , 13 , 15 , 16 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ) , phosphopeptide mapping ( 39 ) , western blotting ( 1 , 2 , 3 , 7 , 10 , 13 , 15 , 16 , 18 , 19 , 20 , 23 , 24 , 25 , 27 , 28 , 31 , 32 , 33 , 34 , 35 , 39 , 40 , 41 )
Disease tissue studied:
kidney cancer ( 19 ) , liver cancer ( 19 ) , tuberous sclerosis ( 19 )
Relevant cell line - cell type - tissue:
'brain, hippocampus, dentate gyrus' ( 1 ) , 'brain, striatum' ( 35 ) , 'neuron, cerebellar granule'-brain ( 27 ) , 'neuron, sympathetic' ( 28 ) , 293 (epithelial) ( 13 , 16 , 39 ) , 32D (myeloid) [IRS1 (mouse)] ( 34 ) , 32Dcl3 (myeloid) [FLT3 (mouse), transfection, chimera with human FLT3-ITD mutant (corresponding to wild type P36888 ( 14 ) , 32Dcl3 (myeloid) ( 14 ) , 3T3 (fibroblast) [INSR (human)] ( 39 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 30 , 34 ) , 3T3 (fibroblast) ( 13 , 23 , 40 ) , brain ( 11 ) , fibroblast-embryo [Jun (mouse)] ( 36 ) , glial ( 19 ) , heart ( 11 ) , HEK293T (epithelial) ( 23 , 27 ) , HeLa (cervical) ( 41 ) , Hepa 1-6 (epithelial) ( 17 ) , JB6 RT101 (epidermal) ( 25 ) , kidney ( 11 , 19 ) , liver ( 19 ) , lung ( 11 ) , macrophage-bone marrow ( 2 , 12 , 15 ) , macrophage-bone marrow [DUSP1 (mouse), homozygous knockout] ( 12 ) , macrophage-peritoneum ( 6 ) , MEF (fibroblast) ( 7 , 9 , 18 , 19 , 20 , 24 , 31 , 32 , 33 , 34 ) , MEF (fibroblast) [IGF1R (mouse)] ( 30 , 37 ) , MEF (fibroblast) [JNK1 (mouse), transfection] ( 16 ) , MEF (fibroblast) [Jun (mouse), homozygous knockout] ( 40 ) , MEF (fibroblast) [p53 (mouse), homozygous knockout] ( 8 ) , MEF (fibroblast) [TSC2 (mouse), homozygous knockout] ( 9 ) , MRC5 (fibroblast) ( 18 ) , myocyte-heart ( 10 ) , NMuMG (epithelial) ( 3 ) , oligodendrocyte ( 22 ) , preosteoclast ( 29 ) , RAW 264 (macrophage) ( 32 ) , RAW 264.7 (macrophage) ( 4 ) , spinal cord ( 1 , 22 ) , synoviocyte ( 38 )

Upstream Regulation
Regulatory protein:
basonuclin 1 (human) ( 3 ) , CTNNB1 (mouse) ( 16 ) , DUSP1 (mouse) ( 2 ) , Fos (mouse) ( 40 ) , JDP2 (mouse) ( 7 ) , JNK1 (human) ( 16 ) , JNK1 (mouse) ( 24 , 25 ) , JNK2 (mouse) ( 24 ) , MST1 (mouse) ( 13 ) , MST2 (mouse) ( 13 ) , PXN (mouse) ( 26 ) , RLF (mouse) ( 39 ) , RRas (mouse) ( 40 ) , Src (mouse) ( 40 ) , TSC2 (mouse) ( 19 )
Putative in vivo kinases:
ERK1 (mouse) ( 32 ) , JNK1 (mouse) ( 13 , 18 , 20 , 30 , 32 , 37 ) , JNK2 (human) ( 18 )
Kinases, in vitro:
JNK1 (human) ( 13 ) , JNK1 (mouse) ( 32 ) , JNK3 (mouse) ( 22 )
Treatments:
anisomycin ( 7 , 32 , 36 ) , Aplidin ( 31 ) , bacterial infection ( 15 ) , botulinum_C3_toxin ( 13 ) , butyrate ( 19 ) , cycloheximide ( 7 ) , EGF ( 26 , 32 ) , GNE-3511 ( 1 ) , GNE-8505 ( 1 ) , hypoxia ( 36 ) , IL-1a ( 18 ) , IL-1b ( 38 ) , IL-33 ( 4 ) , injury ( 22 ) , insulin ( 34 ) , ischemia/reperfusion ( 10 ) , kainic_acid ( 27 ) , KN-62 ( 27 ) , leptomycin_B ( 23 ) , lithium ( 27 ) , LPS ( 2 , 12 , 15 , 32 ) , LY294002 ( 34 ) , metamfetamine ( 35 ) , MG132 ( 7 ) , NGF_withdrawal ( 28 ) , nimodipine ( 27 ) , okadaic_acid ( 23 ) , PD184352 ( 32 ) , PD98059 ( 31 , 34 , 38 ) , phorbol_ester ( 26 , 32 ) , RANKL ( 29 ) , rapamycin ( 19 ) , rottlerin ( 27 ) , SB203580 ( 7 , 31 , 32 , 38 ) , serum ( 7 ) , siRNA ( 26 ) , SP600125 ( 7 , 10 , 13 , 18 , 20 , 33 , 38 ) , TGF-beta ( 3 ) , TNF ( 32 ) , U0126 ( 7 ) , UV ( 7 , 20 , 24 , 25 , 30 , 37 )

Downstream Regulation
Effects of modification on Jun:
acetylation ( 18 ) , activity, induced ( 23 ) , molecular association, regulation ( 18 ) , sumoylation ( 41 )
Effects of modification on biological processes:
apoptosis, induced ( 28 , 31 ) , cell growth, altered ( 40 ) , cell motility, altered ( 33 ) , transcription, altered ( 23 , 28 ) , transcription, induced ( 18 , 41 )
Induce interaction with:
DNA ( 18 ) , NFkB-p65 (human) ( 18 )
Inhibit interaction with:
HDAC3 (human) ( 18 )

Disease / Diagnostics Relevance
Relevant diseases:
non-melanoma skin cancer ( 40 )

References 

1

Le Pichon CE, et al. (2017) Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease. Sci Transl Med 9
28814543   Curated Info

2

McGuire VA, et al. (2017) Beta Interferon Production Is Regulated by p38 Mitogen-Activated Protein Kinase in Macrophages via both MSK1/2- and Tristetraprolin-Dependent Pathways. Mol Cell Biol 37
27795299   Curated Info

3

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

4

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

5

Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20
23684622   Curated Info

6

Wu X, et al. (2012) Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics 11, 1640-51
22942356   Curated Info

7

Weidenfeld-Baranboim K, Koren L, Aronheim A (2011) Phosphorylation of JDP2 on threonine-148 by the c-Jun N-terminal kinase targets it for proteosomal degradation. Biochem J 436, 661-9
21463260   Curated Info

8

Hsu PP, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-22
21659604   Curated Info

9

Yu Y, et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-6
21659605   Curated Info

10

Wei J, et al. (2011) c-Jun N-terminal kinase (JNK-1) confers protection against brief but not extended ischemia during acute myocardial infarction. J Biol Chem 286, 13995-4006
21324895   Curated Info

11

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
21183079   Curated Info

12

Weintz G, et al. (2010) The phosphoproteome of toll-like receptor-activated macrophages. Mol Syst Biol 6, 371
20531401   Curated Info

13

Densham RM, et al. (2009) MST kinases monitor actin cytoskeletal integrity and signal via c-Jun N-terminal kinase stress-activated kinase to regulate p21Waf1/Cip1 stability. Mol Cell Biol 29, 6380-90
19822666   Curated Info

14

Choudhary C, et al. (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326-39
19854140   Curated Info

15

Leng J, et al. (2009) Toxoplasma gondii prevents chromatin remodeling initiated by TLR-triggered macrophage activation. J Immunol 182, 489-97
19109180   Curated Info

16

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

17

Pan C, Gnad F, Olsen JV, Mann M (2008) Quantitative phosphoproteome analysis of a mouse liver cell line reveals specificity of phosphatase inhibitors. Proteomics 8, 4534-46
18846507   Curated Info

18

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

19

Ozcan U, et al. (2008) Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 29, 541-51
18342602   Curated Info

20

Yogev O, et al. (2008) DNA damage-dependent translocation of B23 and p19 ARF is regulated by the Jun N-terminal kinase pathway. Cancer Res 68, 1398-406
18316603   Curated Info

21

Takatori A, et al. (2008) Differential transmission of MEKK1 morphogenetic signals by JNK1 and JNK2. Development 135, 23-32
18032450   Curated Info

22

Li QM, et al. (2007) Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury. J Neurosci 27, 8395-404
17670986   Curated Info

23

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
16964287   Curated Info

24

Jaeschke A, et al. (2006) JNK2 is a positive regulator of the cJun transcription factor. Mol Cell 23, 899-911
16973441   Curated Info

25

Lu C, et al. (2006) Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Mol Cell 23, 121-32
16818236   Curated Info

26

Tatsumi Y, et al. (2006) Involvement of the paxillin pathway in JB6 Cl41 cell transformation. Cancer Res 66, 5968-74
16740738   Curated Info

27

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

28

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

29

Wada T, et al. (2005) The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis. Nat Med 11, 394-9
15750601   Curated Info

30

Sabapathy K, et al. (2004) Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol Cell 15, 713-25
15350216   Curated Info

31

Cuadrado A, et al. (2004) JNK activation is critical for Aplidin-induced apoptosis. Oncogene 23, 4673-80
15122339   Curated Info

32

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
12881422   Curated Info

33

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
12730213   Curated Info

34

Lee YH, Giraud J, Davis RJ, White MF (2003) c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. J Biol Chem 278, 2896-902
12417588   Curated Info

35

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
11961130   Curated Info

36

Laderoute KR, et al. (2002) The response of c-jun/AP-1 to chronic hypoxia is hypoxia-inducible factor 1 alpha dependent. Mol Cell Biol 22, 2515-23
11909946   Curated Info

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
11896587   Curated Info

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
11435459   Curated Info

39

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
11046144   Curated Info

40

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
10851065   Curated Info

41

Muller S, et al. (2000) c-Jun and p53 activity is modulated by SUMO-1 modification. J Biol Chem 275, 13321-9
10788439   Curated Info