Phospho-IRS-1 (Ser318) (D51C3) Rabbit mAb

• 产品编号：CST-5610S      品牌：CST       原厂货号：5610S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-IRS-1 (Ser318) (D51C3) Rabbit mAb用于检测内源性在318位丝氨酸位点磷酸化的IRS-1蛋白水平。请注意：Ser318指的是小鼠蛋白位点，人的对应位点为Ser323位。抗体会在57 kDa处有一个非特异性的诱导性交互反应条带。该单抗通过用对应于鼠源IRS-1蛋白Ser318位点周围残基序列的合成肽免疫动物制备而得。胰岛素受体底物1(IRS-1)是胰岛素受体激酶的一类主要底物(1)。 IRS-1包含多个酪氨酸磷酸化位点，可以作为含SH2结构域蛋白的停靠位点，这些蛋白调控着胰岛素的代谢和促生长功能(2-4)　。IRS-1还包含着起过30个潜在的丝氨酸/苏氨酸磷酸化位点，307位丝氨酸可以被JNK(5)和IKK(6)磷酸化，789位的丝氨酸可以被SIK-2（是AMPK家族成员）磷酸化(7)。PKC和mTOR途径可以分别磷酸化IRS-1的612位丝氨酸和636/639位丝氨酸(8,9)。PKCθ可以介导IRS-2在1101位丝氨酸位的磷酸化，此位点的磷酸化会导致细胞胰岛素信号通路的抑制，因此它可能在某些肥胖模型的胰岛素抵抗中起着某些作用(10)。PKC在胰岛素受体激活或其它的因素刺激下如TPA,IL-6，维甲酸处理下，可以磷酸化鼠IRS-1蛋白318位丝氨酸（人323Ser）（11-14）。该位点的磷酸化是胰岛素通路的反馈信号，反馈抑制胰岛素信号（14-16）。

1. Sun, X.J. et al. (1991) Nature 352, 73-77.
2. Sun, X.J. et al. (1992) J. Biol. Chem. 267, 22662-22672.
3. Myers Jr., M.G. et al. (1993) Endocrinology 132, 1421-1430.
4. Wang, L.M. et al. (1993) Science 261, 1591-1594.
5. Rui, L. et al. (1997) J. Clin. Invest. 107, 181-189.
6. Gao, Z. et al. (2002) J. Biol. Chem. 277, 48115-48121.
7. Horike, N. et al. (2003) J. Biol. Chem. 278, 18440-18447.
8. Ozes, O.N. et al. (2001) Proc. Natl. Acad. Sci. USA 98, 4640-4645.
9. De Fea, K. and Ruth, R.A. (1997) Biochemistry 36, 12939-12947.
10. Li, Y. et al. (2004) J. Biol. Chem. 279, 45304-45307.
11. Greene, M.W. et al. (2004) Biochem J 378, 105-116.
12. Weigert, C. et al. (2006) J Biol Chem 281, 7060-7067.
13. del Rincón, S.V. et al. (2004) Oncogene 23, 9269-9279.
14. Moeschel, K. et al. (2004) J Biol Chem 279, 25157-25163.
15. Weigert, C. et al. (2005) J Biol Chem 280, 37393-37399.
16. Hennige, A.M. et al. (2006) FASEB J 20, 1206-1208.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Rat

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.

Background

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).

1. Sun, X.J. et al. (1991) Nature 352, 73-77.
2. Sun, X.J. et al. (1992) J. Biol. Chem. 267, 22662-22672.
3. Myers Jr., M.G. et al. (1993) Endocrinology 132, 1421-1430.
4. Wang, L.M. et al. (1993) Science 261, 1591-1594.
5. Rui, L. et al. (1997) J. Clin. Invest. 107, 181-189.
6. Gao, Z. et al. (2002) J. Biol. Chem. 277, 48115-48121.
7. Horike, N. et al. (2003) J. Biol. Chem. 278, 18440-18447.
8. Ozes, O.N. et al. (2001) Proc. Natl. Acad. Sci. USA 98, 4640-4645.
9. De Fea, K. and Ruth, R.A. (1997) Biochemistry 36, 12939-12947.
10. Li, Y. et al. (2004) J. Biol. Chem. 279, 45304-45307.
11. Greene, M.W. et al. (2004) Biochem J 378, 105-116.
12. Weigert, C. et al. (2006) J Biol Chem 281, 7060-7067.
13. del Rincón, S.V. et al. (2004) Oncogene 23, 9269-9279.
14. Moeschel, K. et al. (2004) J Biol Chem 279, 25157-25163.
15. Weigert, C. et al. (2005) J Biol Chem 280, 37393-37399.
16. Hennige, A.M. et al. (2006) FASEB J 20, 1206-1208.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody