Ser307
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Home > Phosphorylation Site Page: > Ser307  -  IRS1 (mouse)

Site Information
tEsITAtsPAsMVGG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447558

In vivo Characterization
Methods used to characterize site in vivo:
[32P] ATP in vitro ( 11 ) , [32P] bio-synthetic labeling ( 36 ) , electrophoretic mobility shift ( 30 ) , immunoprecipitation ( 1 ) , mass spectrometry ( 2 , 4 , 6 , 14 ) , mutation of modification site ( 1 , 13 , 36 ) , peptide sequencing ( 26 , 36 ) , phospho-antibody ( 3 , 7 , 9 , 10 , 11 , 12 , 13 , 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ) , western blotting ( 1 , 3 , 7 , 9 , 10 , 11 , 12 , 13 , 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 26 , 29 , 31 , 32 , 33 , 34 , 35 )
Disease tissue studied:
kidney cancer ( 19 ) , liver cancer ( 33 ) , diabetes mellitus ( 20 ) , type 2 diabetes ( 11 , 20 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 4 , 6 ) , 'muscle, skeletal' ( 12 , 13 , 21 , 29 , 35 ) , 293 (epithelial) ( 36 ) , 32D (myeloid) [IRS1 (mouse)] ( 36 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 24 , 28 , 30 , 31 , 32 , 33 ) , 3T3-L1 (fibroblast) ( 20 , 22 ) , adipose tissue ( 15 , 27 ) , adipose tissue [p70S6K (mouse), homozygous knockout] ( 26 ) , aorta ( 18 ) , BAEC (endothelial) ( 19 ) , beta-pancreas [INSR (mouse), transgenic] ( 10 ) , C2C12 (myoblast) ( 7 , 17 , 21 , 23 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 36 ) , HeLa (cervical) ( 26 ) , hepatocyte ( 1 ) , HepG2 (hepatic) ( 33 ) , L6 (myoblast) ( 21 ) , liver ( 21 , 27 ) , liver [p70S6K (mouse), homozygous knockout] ( 26 ) , MC3T3-E1 (preosteoblast) ( 2 ) , MEF (fibroblast) ( 34 ) , MEF (fibroblast) [IGF1R (mouse)] ( 25 , 33 ) , MEF (fibroblast) [JNK1 (mouse), homozygous knockout] ( 11 ) , MEF (fibroblast) [PKR (mouse), homozygous knockout] ( 11 ) , microvessel-kidney ( 19 ) , muscle ( 20 , 27 ) , muscle [p70S6K (mouse), homozygous knockout] ( 26 ) , myoblast ( 21 ) , myocyte-heart ( 9 ) , placenta ( 3 ) , preadipocyte ( 14 )

Upstream Regulation
Regulatory protein:
IRS1 (mouse) ( 16 ) , JIP1 (mouse) ( 27 ) , JNK1 (mouse) ( 9 , 11 ) , Raptor (mouse) ( 7 ) , RHEB (mouse) ( 7 ) , RHOA (mouse) ( 19 ) , ROCK1 (mouse) ( 12 ) , Syk (mouse) ( 19 )
Putative in vivo kinases:
IKKA (mouse) ( 28 ) , JNK1 (mouse) ( 28 ) , mTOR (mouse) ( 7 ) , PKR (mouse) ( 11 )
Kinases, in vitro:
JNK1 (rat) ( 36 ) , PKR (mouse) ( 11 )
Treatments:
15d-PGJ2 ( 25 , 28 ) , adiponectin ( 3 , 17 ) , amino_acids ( 30 ) , anisomycin ( 25 , 30 ) , anti-FcRII ( 19 ) , anti-FcRIII ( 19 ) , aspirin ( 33 ) , bisindolylmaleimide ( 25 ) , calphostin_C ( 28 ) , CRP ( 19 ) , endothelin ( 24 ) , estradiol ( 22 ) , glucose ( 9 , 25 ) , GSK650394 ( 4 ) , HA-1077 ( 23 ) , high-fat diet ( 13 , 26 ) , hypoxia ( 9 ) , hypoxia/reoxygenation ( 9 ) , IL-6 ( 18 , 21 ) , insulin ( 1 , 4 , 6 , 9 , 10 , 12 , 16 , 17 , 22 , 23 , 24 , 25 , 27 , 30 , 34 , 35 ) , ischemia ( 9 ) , JNK_inhibitor_I ( 18 ) , LG268 ( 29 ) , linoleic_acid ( 28 ) , LY294002 ( 4 , 6 ) , MK-2206 ( 4 , 6 ) , okadaic_acid ( 30 ) , osmotic_stress ( 32 ) , palmitate ( 11 ) , PD98059 ( 18 , 25 , 32 ) , phorbol_ester ( 25 , 28 , 31 ) , piceatannol ( 19 ) , rapamycin ( 7 , 10 , 25 , 30 , 32 ) , rosiglitazone ( 20 , 29 , 31 ) , SB203580 ( 25 ) , siRNA ( 16 , 19 ) , SP600125 ( 9 , 19 , 22 , 25 , 28 , 33 ) , thapsigargin ( 11 ) , TNF ( 11 , 23 , 25 , 30 , 33 ) , Torin1 ( 4 ) , wortmannin ( 25 , 32 ) , Y27632 ( 19 , 23 )

Downstream Regulation
Effects of modification on IRS1:
phosphorylation ( 36 )
Effects of modification on biological processes:
cell differentiation, inhibited ( 7 ) , signaling pathway regulation ( 7 )

Disease / Diagnostics Relevance
Relevant diseases:
type 2 diabetes ( 20 )

References 

1

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

2

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

3

Aye IL, Rosario FJ, Powell TL, Jansson T (2015) Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth. Proc Natl Acad Sci U S A 112, 12858-63
26417088   Curated Info

4

Parker BL, et al. (2015) Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Sci Signal 8, rs6
26060331   Curated Info

5

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

6

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

7

Ge Y, Yoon MS, Chen J (2011) Raptor and Rheb negatively regulate skeletal myogenesis through suppression of insulin receptor substrate 1 (IRS1). J Biol Chem 286, 35675-82
21852229   Curated Info

8

Wen H, et al. (2011) Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 12, 408-15
21478880   Curated Info

9

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

10

Bartolomé A, Guillén C, Benito M (2010) Role of the TSC1-TSC2 complex in the integration of insulin and glucose signaling involved in pancreatic beta-cell proliferation. Endocrinology 151, 3084-94
20427478   Curated Info

11

Nakamura T, et al. (2010) Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140, 338-48
20144759   Curated Info

12

Lee DH, et al. (2009) Targeted disruption of ROCK1 causes insulin resistance in vivo. J Biol Chem 284, 11776-80
19276091   Curated Info

13

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

14

Krüger M, et al. (2008) Dissection of the insulin signaling pathway via quantitative phosphoproteomics. Proc Natl Acad Sci U S A 105, 2451-6
18268350   Curated Info

15

Jaeschke A, Davis RJ (2007) Metabolic stress signaling mediated by mixed-lineage kinases. Mol Cell 27, 498-508
17679097   Curated Info

16

Shahid G, Hussain T (2007) GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells. J Biol Chem 282, 20612-20
17517892   Curated Info

17

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

18

Andreozzi F, et al. (2007) Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Mol Cell Biol 27, 2372-83
17242212   Curated Info

19

Xu JW, et al. (2007) C-reactive protein suppresses insulin signaling in endothelial cells: role of spleen tyrosine kinase. Mol Endocrinol 21, 564-73
17095576   Curated Info

20

Wang X, et al. (2006) Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology 147, 4160-8
16777975   Curated Info

21

Weigert C, et al. (2006) Direct cross-talk of interleukin-6 and insulin signal transduction via insulin receptor substrate-1 in skeletal muscle cells. J Biol Chem 281, 7060-7
16418171   Curated Info

22

Nagira K, et al. (2006) Altered subcellular distribution of estrogen receptor alpha is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes. Endocrinology 147, 1020-8
16269459   Curated Info

23

Kanda T, et al. (2006) Rho-kinase as a molecular target for insulin resistance and hypertension. FASEB J 20, 169-71
16267124   Curated Info

24

Usui I, et al. (2005) G protein-coupled receptor kinase 2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes. Mol Endocrinol 19, 2760-8
15994203   Curated Info

25

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

26

Um SH, et al. (2004) Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431, 200-5
15306821   Curated Info

27

Jaeschke A, Czech MP, Davis RJ (2004) An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue. Genes Dev 18, 1976-80
15314024   Curated Info

28

Gao Z, et al. (2004) Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Mol Endocrinol 18, 2024-34
15143153   Curated Info

29

Shen Q, et al. (2004) Effects of rexinoids on glucose transport and insulin-mediated signaling in skeletal muscles of diabetic (db/db) mice. J Biol Chem 279, 19721-31
14998989   Curated Info

30

Carlson CJ, White MF, Rondinone CM (2004) Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation. Biochem Biophys Res Commun 316, 533-9
15020250   Curated Info

31

Jiang G, et al. (2004) Rosiglitazone, an agonist of peroxisome-proliferator-activated receptor gamma (PPARgamma), decreases inhibitory serine phosphorylation of IRS1 in vitro and in vivo. Biochem J 377, 339-46
14556646   Curated Info

32

Gual P, et al. (2003) Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes. J Biol Chem 278, 26550-7
12730242   Curated Info

33

Gao Z, et al. (2003) Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in tumor necrosis factor-treated cells through targeting multiple serine kinases. J Biol Chem 278, 24944-50
12714600   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

Rui L, et al. (2001) Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest 107, 181-9
11160134   Curated Info

36

Aguirre V, et al. (2000) The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem 275, 9047-54
10722755   Curated Info