Anti- IRS-1 (Ab-636) Antibody (GWB-33F624)

GWB-33F624

18-785-210231

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Description

Binding Site: around Ser636 WB Dilution: 500~1000

IHC Dilution: 50~100 Function: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).

Subunit: Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR via the PTB domain. Binds to phosphatidylinositol 3-kinase p85 subunit via the phosphorylated YXXM motifs. Binds ROCK1. Binds to UBTF and PIK3CA in nuclear extracts (By similarity). Interacts with SOCS7.

Ptm: Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity).

Ptm: Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity).

Polymorphism: The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance.

Disease: Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853].

Similarity: Contains 1 IRS-type PTB domain.

Similarity: Contains 1 PH domain. [1] Araki E., Sun X.J., Haag B.L. III, Chuang L.M., Zhang Y., Yang-Feng T.L., White M.F., Kahn C.R.
Human skeletal muscle insulin receptor substrate-1. Characterization of the cDNA, gene, and chromosomal localization.
[2] Nishiyama M., Wands J.R.
Cloning and increased expression of an insulin receptor substrate-1-like gene in human hepatocellular carcinoma.
[3] Smith L.K., Bradshaw M., Croall D.E., Garner C.W.
The insulin receptor substrate (IRS-1) is a PEST protein that is susceptible to calpain degradation in vitro.
[4] Craparo A., O\'Neill T.J., Gustafson T.A.
Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor.
[5] He W., O\'Neill T.J., Gustafson T.A.
Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains.
[6] Gustafson T.A., He W., Craparo A., Schaub C.D., O\'Neill T.J.
Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain.
[7] Horike N., Takemori H., Katoh Y., Doi J., Min L., Asano T., Sun X.J., Yamamoto H., Kasayama S., Muraoka M., et al.
Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2.
[8] Banks A.S., Li J., McKeag L., Hribal M.L., Kashiwada M., Accili D., Rothman P.B.
Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans.
[9] Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J., et al.
Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.
[10] Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

Additional Information

Name Anti- IRS-1 (Ab-636) Antibody (GWB-33F624)
Availability In Stock
Related Product Names IRS-1 IRS-1 (Ab-636)IRS-1
Swissprot ID P35568
Molecular Weight 131591
Purity Affinity Purified
Source Rabbit
Application IHC, WB
Clonality Polyclonal
Format In PBS, 0.02% sodium azide and 50% glycerol.
Stability 1 year at -20C
Reactivity Human, Mouse, Rat
Storage 4C for short term (weeks) and -20C for long term. Avoid frequent freeze and thaw.
Datasheets/Manuals Printable datasheet for GWB-33F624
Intended Use Research Use Only