Ser635
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Home > Phosphorylation Site Page: > Ser635  -  IRS1 (mouse)

Site Information
yMPMsPKsVsAPQQI   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447507

In vivo Characterization
Methods used to characterize site in vivo:
mass spectrometry ( 1 , 9 , 11 ) , mutation of modification site ( 9 ) , peptide sequencing ( 10 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ) , western blotting ( 2 , 3 , 4 , 5 , 6 , 7 , 10 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 1 , 3 ) , 'muscle, skeletal' ( 4 ) , 293 (epithelial) ( 7 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 8 ) , 3T3-L1 (fibroblast) ( 2 ) , adipose tissue [p70S6K (mouse), homozygous knockout] ( 10 ) , C2C12 (myoblast) ( 5 , 6 ) , C3H10T1/2 (fibroblast) ( 11 ) , H9c2 (myoblast) ( 5 ) , HeLa (cervical) ( 10 ) , keratinocyte-skin [IGF1 (mouse)] ( 7 ) , L6 (myoblast) ( 2 ) , liver [p70S6K (mouse), homozygous knockout] ( 10 ) , MEF (fibroblast) ( 2 ) , muscle [p70S6K (mouse), homozygous knockout] ( 10 )

Upstream Regulation
Regulatory protein:
ROCK1 (mouse) ( 4 ) , Sin1 (human) ( 2 )
Putative in vivo kinases:
GRK2 (mouse) ( 8 ) , mTOR (human) ( 2 ) , ROCK1 (rat) ( 5 ) , ROCK2 (mouse) ( 9 )
Kinases, in vitro:
mTOR (mouse) ( 11 ) , ROCK2 (mouse) ( 9 )
Treatments:
adiponectin ( 6 ) , dactolisib ( 2 ) , endothelin ( 8 ) , high-fat diet ( 10 ) , IGF-1 ( 2 , 7 ) , insulin ( 1 , 2 , 4 , 6 , 8 , 9 ) , MG132 ( 2 ) , rapamycin ( 2 , 6 , 7 , 9 , 11 ) , serum ( 2 ) , serum_withdrawal ( 5 ) , siRNA ( 2 , 9 ) , TNF ( 3 , 11 ) , Torin1 ( 2 ) , troglitazone ( 7 ) , Y27632 ( 9 )

Downstream Regulation
Effects of modification on IRS1:
protein degradation ( 2 , 8 )

References 

1

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

2

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

3

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

4

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

5

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

6

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

7

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

8

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

9

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

10

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

11

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