Ser639
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Home > Phosphorylation Site Page: > Ser639  -  IRS1 (human)

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:
immunoprecipitation ( 9 ) , mass spectrometry ( 10 ) , mutation of modification site ( 12 ) , phospho-antibody ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 18 ) , western blotting ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 15 , 16 )
Disease tissue studied:
breast cancer ( 4 , 5 , 7 ) , colorectal cancer ( 8 ) , colorectal carcinoma ( 8 ) , liver cancer ( 15 ) , lung cancer ( 8 ) , non-small cell lung cancer ( 8 ) , non-small cell squamous cell lung carcinoma ( 8 ) , diabetes mellitus ( 7 ) , type 2 diabetes ( 7 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
Akt1 (human) ( 6 ) , Akt2 (human) ( 6 ) , LKB1 (human) ( 8 ) , LST8 (human) ( 6 ) , mTOR (human) ( 6 , 12 ) , p70S6K (human) ( 6 , 12 , 17 ) , P70S6KB (human) ( 12 ) , PDK1 (human) ( 6 ) , PIK3CA (human) ( 6 ) , Raptor (human) ( 6 ) , RHEB (human) ( 12 ) , RICTOR (human) ( 6 ) , Sin1 (human) ( 6 ) , TSC1 (human) ( 7 ) , TSC1 (mouse) ( 12 ) , TSC2 (mouse) ( 12 )
Putative in vivo kinases:
p70S6K (mouse) ( 12 )
Kinases, in vitro:
ERK2 (human) ( 9 )
Treatments:
4-HT ( 5 ) , 9cRA ( 5 ) , Akt_inhibitor_VIII ( 6 ) , amino_acids ( 14 ) , anisomycin ( 13 ) , carbachol ( 18 ) , dexamethasone ( 5 ) , insulin ( 6 , 10 , 13 , 14 , 15 , 16 , 17 , 18 ) , LY294002 ( 6 ) , metformin ( 4 ) , okadaic_acid ( 18 ) , PDGF ( 18 ) , rapamycin ( 4 , 6 , 12 , 13 , 14 , 15 , 16 ) , retinoic_acid ( 5 ) , serum ( 6 ) , siRNA ( 8 , 17 ) , SP600125 ( 13 ) , tamoxifen ( 5 ) , TNF ( 7 ) , wortmannin ( 6 )

Downstream Regulation
Effects of modification on IRS1:
intracellular localization ( 12 )

References 

1

Fang X, et al. (2019) Isoflurane aggravates peripheral and central insulin resistance in high-fat diet/streptozocin-induced type 2 diabetic mice. Brain Res, 146511
31672472   Curated Info

2

Koh A, et al. (2018) Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. Cell 175, 947-961.e17
30401435   Curated Info

3

Garwood CJ, et al. (2015) Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors. Mol Brain 8, 51
26297026   Curated Info

4

Zakikhani M, Blouin MJ, Piura E, Pollak MN (2010) Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Cancer Res Treat 123, 271-9
20135346   Curated Info

5

Eto I (2010) Upstream molecular signaling pathways of p27(Kip1) expression: Effects of 4-hydroxytamoxifen, dexamethasone, and retinoic acids. Cancer Cell Int 10, 3
20170512   Curated Info

6

Tzatsos A (2009) Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR. J Biol Chem 284, 22525-34
19561084   Curated Info

7

Lee DF, et al. (2008) IKKbeta suppression of TSC1 function links the mTOR pathway with insulin resistance. Int J Mol Med 22, 633-8
18949383   Curated Info

8

Zhong D, et al. (2008) LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res 68, 7270-7
18794113   Curated Info

9

Luo M, et al. (2007) Phosphorylation of human insulin receptor substrate-1 at Serine 629 plays a positive role in insulin signaling. Endocrinology 148, 4895-905
17640984   Curated Info

10

Yi Z, et al. (2007) Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle. Diabetes 56, 1508-16
17360977   Curated Info

11

Vander Haar E, et al. (2007) Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol 9, 316-23
17277771   Curated Info

12

Shah OJ, Hunter T (2006) Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol 26, 6425-34
16914728   Curated Info

13

Hiratani K, et al. (2005) Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation of IRS-1. Biochem Biophys Res Commun 335, 836-42
16099428   Curated Info

14

Tremblay F, et al. (2005) Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 54, 2674-84
16123357   Curated Info

15

Khamzina L, Veilleux A, Bergeron S, Marette A (2005) Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance. Endocrinology 146, 1473-81
15604215   Curated Info

16

Tremblay F, et al. (2005) Activation of the mammalian target of rapamycin pathway acutely inhibits insulin signaling to Akt and glucose transport in 3T3-L1 and human adipocytes. Endocrinology 146, 1328-37
15576463   Curated Info

17

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

18

Batty IH, Fleming IN, Downes CP (2004) Muscarinic-receptor-mediated inhibition of insulin-like growth factor-1 receptor-stimulated phosphoinositide 3-kinase signalling in 1321N1 astrocytoma cells. Biochem J 379, 641-51
14769130   Curated Info