Ser632
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Home > Phosphorylation Site Page: > Ser632  -  IRS1 (mouse)

Site Information
NGDyMPMsPKsVsAP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447506

In vivo Characterization
Methods used to characterize site in vivo:
mass spectrometry ( 1 , 2 , 3 , 5 , 7 , 10 , 14 , 17 , 19 ) , mutation of modification site ( 17 , 20 ) , peptide sequencing ( 18 ) , phospho-antibody ( 4 , 6 , 8 , 9 , 12 , 13 , 15 , 16 , 17 ) , western blotting ( 4 , 6 , 8 , 9 , 12 , 13 , 15 , 16 , 18 )
Disease tissue studied:
liver cancer ( 9 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 2 , 3 , 6 ) , 'fat, brown' ( 7 ) , 'muscle, skeletal' ( 8 ) , 293 (epithelial) ( 9 , 15 ) , 3T3 (fibroblast) ( 9 ) , 3T3-L1 (fibroblast) ( 4 , 9 , 16 , 20 ) , adipose tissue [p70S6K (mouse), homozygous knockout] ( 18 ) , C2C12 (myoblast) ( 12 , 13 ) , C2C12-D (muscle cell) ( 14 ) , C3H10T1/2 (fibroblast) ( 19 ) , H4IIe (hepatic) ( 9 ) , H9c2 (myoblast) ( 12 ) , HeLa (cervical) ( 18 ) , Hepa 1-6 (epithelial) ( 10 ) , keratinocyte-skin [IGF1 (mouse)] ( 15 ) , L6 (myoblast) ( 4 ) , liver [p70S6K (mouse), homozygous knockout] ( 18 ) , MC3T3-E1 (preosteoblast) ( 1 ) , MEF (fibroblast) ( 4 , 5 ) , muscle [p70S6K (mouse), homozygous knockout] ( 18 )

Upstream Regulation
Regulatory protein:
Akt1 (mouse) ( 20 ) , ROCK1 (mouse) ( 8 ) , Sin1 (human) ( 4 )
Putative in vivo kinases:
mTOR (human) ( 4 ) , ROCK1 (rat) ( 12 ) , ROCK2 (mouse) ( 17 )
Kinases, in vitro:
mTOR (mouse) ( 19 ) , ROCK2 (mouse) ( 17 )
Treatments:
adiponectin ( 13 ) , dactolisib ( 4 ) , estradiol ( 16 ) , high-fat diet ( 18 ) , IGF-1 ( 4 , 15 ) , insulin ( 2 , 3 , 4 , 8 , 13 , 16 , 17 ) , MG132 ( 4 ) , PDGF ( 20 ) , PTH(1-34) ( 1 ) , rapamycin ( 4 , 13 , 15 , 17 , 19 ) , serum ( 4 ) , serum_withdrawal ( 12 ) , siRNA ( 4 , 17 ) , TNF ( 6 , 19 ) , Torin1 ( 4 ) , troglitazone ( 15 ) , Y27632 ( 17 )

Downstream Regulation
Effects of modification on IRS1:
molecular association, regulation ( 20 ) , protein degradation ( 4 )
Inhibit interaction with:
PIK3C2A (mouse) ( 20 )

Disease / Diagnostics Relevance
Relevant diseases:
obesity, hyperphagic ( 9 )

References 

1

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

2

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

3

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

4

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

5

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

6

Nohara A, et al. (2011) Cyclin-dependent kinase-5 is a key molecule in tumor necrosis factor-α-induced insulin resistance. J Biol Chem 286, 33457-65
21813649   Curated Info

7

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

8

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

9

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

10

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

11

Mertins P, et al. (2008) Investigation of protein-tyrosine phosphatase 1B function by quantitative proteomics. Mol Cell Proteomics 7, 1763-77
18515860   Curated Info

12

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

13

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

14

Guo A (2007) CST Curation Set: 2565; Year: 2007; Biosample/Treatment: cell line, C2C12-D/Insulin; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

15

He G, Sung YM, Digiovanni J, Fischer SM (2006) Thiazolidinediones inhibit insulin-like growth factor-i-induced activation of p70S6 kinase and suppress insulin-like growth factor-I tumor-promoting activity. Cancer Res 66, 1873-8
16452250   Curated Info

16

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

17

Furukawa N, et al. (2005) Role of Rho-kinase in regulation of insulin action and glucose homeostasis. Cell Metab 2, 119-29
16098829   Curated Info

18

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

19

Ozes ON, et al. (2001) A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc Natl Acad Sci U S A 98, 4640-5
11287630   Curated Info

20

Li J, DeFea K, Roth RA (1999) Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J Biol Chem 274, 9351-6
10092613   Curated Info