Ser302
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Home > Phosphorylation Site Page: > Ser302  -  IRS1 (mouse)

Site Information
TRRSRtEsITAtsPA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 450190

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 2 ) , mass spectrometry ( 1 , 3 , 5 ) , mutation of modification site ( 2 , 9 , 15 ) , phospho-antibody ( 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ) , western blotting ( 2 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 )
Disease tissue studied:
liver cancer ( 8 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 1 , 5 ) , 'fat, brown'-'fat, brown' ( 7 ) , 'muscle, skeletal' ( 7 , 9 , 15 ) , 293 (epithelial) ( 8 ) , 32D (myeloid) [IRS1 (mouse)] ( 15 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 15 ) , 3T3 (fibroblast) ( 8 ) , 3T3-L1 (fibroblast) ( 6 , 8 , 14 ) , adipocyte ( 12 ) , beta-pancreas ( 13 ) , C2C12 (myoblast) ( 10 , 11 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 15 ) , H4IIe (hepatic) ( 8 ) , H9c2 (myoblast) ( 10 ) , hepatocyte ( 2 ) , hepatocyte-liver ( 13 ) , HUVEC (endothelial) ( 12 ) , liver ( 7 ) , MC3T3-E1 (preosteoblast) ( 3 ) , MEF (fibroblast) ( 6 ) , preadipocyte ( 12 )

Upstream Regulation
Regulatory protein:
FOXO1A (mouse) ( 12 ) , IKKG (mouse) ( 14 ) , MYO1C (mouse) ( 14 ) , RICTOR (mouse) ( 7 ) , Sin1 (human) ( 6 ) , TSC1 (mouse) ( 2 )
Putative in vivo kinases:
mTOR (human) ( 6 ) , ROCK1 (rat) ( 10 )
Treatments:
adiponectin ( 11 ) , amino_acids ( 15 ) , EGF ( 15 ) , FGF2 ( 10 ) , glucose ( 15 ) , IGF-1 ( 15 ) , insulin ( 2 , 5 , 7 , 11 , 14 , 15 ) , JNK_inhibitor_I ( 13 ) , LY294002 ( 5 , 15 ) , MK-2206 ( 5 ) , okadaic_acid ( 15 ) , palmitate ( 13 ) , PD98059 ( 15 ) , PDGF ( 15 ) , rapamycin ( 6 , 11 , 15 ) , serum ( 6 ) , serum_withdrawal ( 10 ) , siRNA ( 6 , 14 ) , TNF ( 14 , 15 ) , Torin1 ( 6 ) , Y27632 ( 10 )

Downstream Regulation
Effects of modification on IRS1:
phosphorylation ( 15 )
Effects of modification on biological processes:
cell growth, altered ( 15 ) , signaling pathway regulation ( 7 )

Disease / Diagnostics Relevance
Relevant diseases:
obesity, hyperphagic ( 8 )

References 

1

Minard AY, et al. (2016) mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. Cell Rep 17, 29-36
27681418   Curated Info

2

Copps KD, Hançer NJ, Qiu W, White MF (2016) Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase. J Biol Chem 291, 8602-17
26846849   Curated Info

3

Williams GR, et al. (2016) Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics. Methods 92, 36-50
26160508   Curated Info

4

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
24719451   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

Kim SJ, et al. (2012) mTOR Complex 2 Regulates Proper Turnover of Insulin Receptor Substrate-1 via the Ubiquitin Ligase Subunit Fbw8. Mol Cell 48, 875-87
23142081   Curated Info

7

Kumar A, et al. (2010) Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism. Diabetes 59, 1397-406
20332342   Curated Info

8

Zhang J, et al. (2008) S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem 283, 35375-82
18952604   Curated Info

9

Morino K, et al. (2008) Muscle-specific IRS-1 Ser->Ala transgenic mice are protected from fat-induced insulin resistance in skeletal muscle. Diabetes 57, 2644-51
18633112   Curated Info

10

Lim MJ, et al. (2007) RhoA/Rho kinase blocks muscle differentiation via serine phosphorylation of insulin receptor substrate-1 and -2. Mol Endocrinol 21, 2282-93
17579208   Curated Info

11

Wang C, et al. (2007) Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1. J Biol Chem 282, 7991-6
17244624   Curated Info

12

Cao Y, et al. (2006) Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. J Biol Chem 281, 40242-51
17077083   Curated Info

13

Solinas G, et al. (2006) Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates. Proc Natl Acad Sci U S A 103, 16454-9
17050683   Curated Info

14

Nakamori Y, et al. (2006) Myosin motor Myo1c and its receptor NEMO/IKK-gamma promote TNF-alpha-induced serine307 phosphorylation of IRS-1. J Cell Biol 173, 665-71
16754954   Curated Info

15

Giraud J, Leshan R, Lee YH, White MF (2004) Nutrient-dependent and insulin-stimulated phosphorylation of insulin receptor substrate-1 on serine 302 correlates with increased insulin signaling. J Biol Chem 279, 3447-54
14623899   Curated Info