Product Pathways - Metabolism
Phospho-IRS-1 (Ser318) (D51C3) Rabbit mAb #5610
|W IP||H M (R)||Endogenous||180||Rabbit IgG|
Reactivity Key: H=Human M=Mouse R=Rat
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.
Specificity / Sensitivity
Phospho-IRS-1 (Ser318) (D51C3) Rabbit mAb recognizes endogenous levels of IRS-1 protein only when phosphorylated at Ser318. Note: Ser318 is the mouse residue; the corresponding human residue is Ser323. The antibody cross reacts with a inducible nonspecific band at around 57 kDa.
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser318 of mouse IRS-1 protein.
Insulin receptor substrate 1 (IRS-1) is one of the major substrates of the insulin receptor kinase (1). IRS-1 contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2-domain containing proteins that mediate the metabolic and growth-promoting functions of insulin (2-4). IRS-1 also contains over 30 potential serine/threonine phosphorylation sites. Ser307 of IRS-1 is phosphorylated by JNK (5) and IKK (6) while Ser789 is phosphorylated by SIK-2, a member of the AMPK family (7). The PKC and mTOR pathways mediate phosphorylation of IRS-1 at Ser612 and Ser636/639, respectively (8,9). Phosphorylation of IRS-1 at Ser1101 is mediated by PKCθ and results in an inhibition of insulin signaling in the cell, suggesting a potential mechanism for insulin resistance in some models of obesity (10).
PKC phosphorylates mouse IRS-1 at Ser318 (human Ser323) by insulin receptor activation or by other stimulation such as TPA, IL-6, retinoic acid treatment (11-14) . The phosphorylation at Ser318 acts as a negative feedback signal to down regulates of insulin effect (14-16).
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- Gao, Z. et al. (2002) J. Biol. Chem. 277, 48115-48121.
- Horike, N. et al. (2003) J. Biol. Chem. 278, 18440-18447.
- Ozes, O.N. et al. (2001) Proc. Natl. Acad. Sci. USA 98, 4640-4645.
- De Fea, K. and Ruth, R.A. (1997) Biochemistry 36, 12939-12947.
- Li, Y. et al. (2004) J. Biol. Chem. 279, 45304-45307.
- Greene, M.W. et al. (2004) Biochem J 378, 105-116.
- Weigert, C. et al. (2006) J Biol Chem 281, 7060-7067.
- del Rincón, S.V. et al. (2004) Oncogene 23, 9269-9279.
- Moeschel, K. et al. (2004) J Biol Chem 279, 25157-25163.
- Weigert, C. et al. (2005) J Biol Chem 280, 37393-37399.
- Hennige, A.M. et al. (2006) FASEB J 20, 1206-1208.
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For Research Use Only. Not For Use In Diagnostic Procedures.