IRS1

From Wikipedia, the free encyclopedia

Insulin receptor substrate 1

PDB rendering based on 1irs.

Available structures: 1irs, 1qqg

Identifiers

Symbol(s)

IRS1; HIRS-1

External IDs

OMIM: 147545 MGI: 99454 HomoloGene: 4049

Gene ontology
Molecular Function:	• signal transducer activity • transmembrane receptor protein tyrosine kinase docking protein activity • insulin receptor binding • insulin-like growth factor receptor binding • protein binding • protein kinase binding • SH2 domain binding • phosphoinositide 3-kinase binding
Cellular Component:	• nucleus • cytoplasm • microsome
Biological Process:	• signal transduction • insulin receptor signaling pathway • insulin-like growth factor receptor signaling pathway

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_005544 (mRNA)
NP_005535 (protein)

NM_010570 (mRNA)
NP_034700 (protein)

Location

Chr 2: 227.31 - 227.37 Mb

Chr 1: 82.12 - 82.17 Mb

Pubmed search

[1]

[2]

Insulin receptor substrate 1 (IRS-1) plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 (IGF-1) receptors to intracellular pathways PI3K / Akt and Erk MAP kinase pathways.

Tyrosine phosphorylation of the insulin or IGF-1 receptors upon ligand binding induces the binding of IRS-1 through its SH2 homology domains. It is then itself tyrosine phosphorylated at numerous residues by these receptors, which enables it to activate several signalling pathways, including the PI3K pathway and the MAP kinase pathway.

IRS-1 plays important biological function for both metabolic and mitogenic (growth promoting) pathways: mice deficent of IRS1 have only a mild diabetic phenotype, but a pronounced growth impairment, i.e. IRS-1 knockout mice only reach 50% of the weight of normal mice. IRS-1 may also play a role in cancer, as it has been shown that transgenic mice overexpressing IRS-1 develop breast cancer.^[1]

[edit] Regulation of IRS-1

The cellular protein levels of IRS-1 are regulated by the Cullin7 E3 ubiquin ligase, which targets IRS-1 for ubiquitin mediated degradation by the proteasome.^[2]

[edit] Further reading

Jiang H, Harris MB, Rothman P (2000). "IL-4/IL-13 signaling beyond JAK/STAT.". J. Allergy Clin. Immunol. 105 (6 Pt 1): 1063–70. PMID 10856136.
Bezerra RM, Chadid TT, Altemani CM, et al. (2004). "Lack of Arg972 polymorphism in the IRS1 gene in Parakanã Brazilian Indians.". Hum. Biol. 76 (1): 147–51. PMID 15222685.
Gibson SL, Ma Z, Shaw LM (2007). "Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis.". Cell Cycle 6 (6): 631–7. PMID 17361103.
Dearth RK, Cui X, Kim HJ, et al. (2007). "Oncogenic transformation by the signaling adaptor proteins insulin receptor substrate (IRS)-1 and IRS-2.". Cell Cycle 6 (6): 705–13. PMID 17374994.

[edit] References

^ Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X, Divisova J, Britton OL, Mohsin S, Allred DC, Hadsell DL, Lee AV. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol. 2006 Dec;26(24):9302-14.
^ Xu X , Sarikas A, Dias-Santagata DC, Dolios G, Lafontant PJ, Tsai SC, Zhu W, Nakajima H, Nakajima HO, Field LJ, Wang R, Pan ZQ. The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell. 2008;30:403-414.