Tyr999
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Phosphorylation Site Page:
Tyr999 - InsR (human)

Site Information
YASSNPEyLSASDVF    SwissProt Entrez-Gene
Predicted information: Scansite
Orthologous residues: InsR (mouse): Y989, InsR (rat): Y1000, InsR iso2 (human): Y987
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447685

In vivo Characterization
Methods used to characterize site in vivo: immunoprecipitation (13), microscopy-colocalization with upstream kinase (9), mutation of modification site (6, 11, 12, 13, 14), phospho-antibody (1, 2, 3, 4, 12, 13), western blotting (1, 2, 3, 9)
Disease tissue studied: liver cancer (2)
Relevant cell line - cell type - tissue: 293 (epithelial) (2), 3T3 (fibroblast) (3), 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] (6), 3T3-L1 (fibroblast) (9), CHO (fibroblast) (14), CHO (fibroblast) [EphB1 (human), transfection] (4, 12, 13), CHO-IR (fibroblast) (11), COS (fibroblast) (6, 9), Huh7 (hepatic) (2), HUVEC (endothelial) (1)

Controlled by
Regulatory protein: Grb14 (human) (2), PTP1B (human) (2)
Kinases, in vitro: InsR (human) (7, 13, 15)
Treatments: IGF-1 (3), IGF-2 (3), IL-6 (1), insulin (1, 2, 3, 4, 12, 13), JNK inhibitor I (1), PD98059 (1), phorbol ester (12)

Downstream Regulation
Effects of modification on InsR: activity, induced (11, 14), enzymatic activity, induced (7), molecular association, regulation (6, 9), phosphorylation (11, 14), receptor internalization, altered (13)
Effects of modification on biological processes: cell cycle regulation (14)
Induce interaction with: SOCS3 (human) (6, 9)


References

1

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

2

Nouaille S, et al. (2006) Interaction with Grb14 results in site-specific regulation of tyrosine phosphorylation of the insulin receptor. EMBO Rep 7, 512-8
16582879   Curated Info

3

Denley A, et al. (2006) Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain. Endocrinology 147, 1029-36
16239300   Curated Info

4

Wick KR, et al. (2003) Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor. J Biol Chem 278, 8460-7
12493740   Curated Info

5

Le MN, Kohanski RA, Wang LH, Sadowski HB (2002) Dual mechanism of signal transducer and activator of transcription 5 activation by the insulin receptor. Mol Endocrinol 16, 2764-79
12456798   Curated Info

6

Peraldi P, et al. (2001) Insulin induces suppressor of cytokine signaling-3 tyrosine phosphorylation through janus-activated kinase. J Biol Chem 276, 24614-20
11325969   Curated Info

7

Noelle V, Tennagels N, Klein HW (2000) A single substitution of the insulin receptor kinase inhibits serine autophosphorylation in vitro: evidence for an interaction between the C-terminus and the activation loop. Biochemistry 39, 7170-7
10852715   Curated Info

8

Soni P, et al. (2000) The differential effects of pp120 (Ceacam 1) on the mitogenic action of insulin and insulin-like growth factor 1 are regulated by the nonconserved tyrosine 1316 in the insulin receptor. Mol Cell Biol 20, 3896-905
10805733   Curated Info

9

Emanuelli B, et al. (2000) SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem 275, 15985-91
10821852   Curated Info

10

van der Geer P, Wiley S, Pawson T (1999) Re-engineering the target specificity of the insulin receptor by modification of a PTB domain binding site. Oncogene 18, 3071-5
10340378   Curated Info

11

Yonezawa K, et al. (1994) Signal transduction pathways from insulin receptors to Ras. Analysis by mutant insulin receptors. J Biol Chem 269, 4634-40
7508445   Curated Info

12

Kaburagi Y, et al. (1993) Site-directed mutagenesis of the juxtamembrane domain of the human insulin receptor. J Biol Chem 268, 16610-22
8393870   Curated Info

13

Murakami MS, Rosen OM (1991) The role of insulin receptor autophosphorylation in signal transduction. J Biol Chem 266, 22653-60
1658004   Curated Info

14

Backer JM, et al. (1991) Cytoplasmic juxtamembrane region of the insulin receptor: a critical role in ATP binding, endogenous substrate phosphorylation, and insulin-stimulated bioeffects in CHO cells. Biochemistry 30, 6366-72
1647198   Curated Info

15

Tavaré JM, Denton RM (1988) Studies on the autophosphorylation of the insulin receptor from human placenta. Analysis of the sites phosphorylated by two-dimensional peptide mapping. Biochem J 252, 607-15
3166375   Curated Info

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