Phospho-IRS-1 (Ser302) Antibody

• 产品编号：CST-2384S      品牌：CST       原厂货号：2384S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-IRS-1 (Ser 302)抗体识别内源性的Ser302磷酸化的鼠IRS-1或Ser307磷酸化的人IRS-1。此抗体不与其它部位磷酸化的IRS-1蛋白发生交叉反应。该多克隆抗体用与鼠IRS-1中Ser302位点附近的氨基酸序列对应的人工合成肽段免疫动物而制成。该抗体使用蛋白A和蛋白亲和层析纯化而得。

胰岛素受体底物1（IRS-1）是胰岛素受体激酶的主要底物之一（1）。IRS-1包括多个酪氨酸磷酸化模体，作为与包含SH2结构域的蛋白质的接合位点，介导胰岛素的代谢和生长促进功能（2-4）。IRS-1也包含超过30个潜在的丝氨酸/苏氨酸磷酸化位点。JNK（5）和IKK（6）对IRS-1 Ser307位点进行磷酸化，SIK2（AMPK家族成员之一）对Ser789进行磷酸化（7）。PKC和mTOR途径分别介导IRS-1的Ser612和Ser636/639磷酸化（8,9）。IRS-1在Ser1101的磷酸化由PKCθ介导，可以导致细胞内胰岛素信号通路的抑制，这暗示其在某些肥胖模型中的胰岛素抵抗机制中发挥作用（10）。大鼠/小鼠IRS-1的Ser302（对应人IRS-1的Ser307）在胰岛素刺激时被快速磷酸化，在IRS-1酪氨酸磷酸化中扮演积极作用。用短期氨基酸/葡萄糖饥饿来抑制Ser302的磷酸化与IRS-1酪氨酸磷酸化下降相关，并且不伴有胰岛素受体自身磷酸化或Akt磷酸化的抑制。这种正向调节通路的抑制对胰岛素抵抗的机制有积极作用（11）。

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. White, M. F. et al. (2004) J. Biol. Chem. 279, 3447-3454.

原厂资料：

Homology

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

Specificity / Sensitivity

Phospho-IRS-1 (Ser 302) Antibody detects endogenous levels of IRS-1 only when phosphorylated at Ser302 of mouse IRS-1 or Ser307 of human IRS-1. This antibody does not detect IRS-1 phosphorylated at other sites.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser 302 of mouse IRS-1. Antibodies are purified by protein A and peptide affinity chromatography.

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).Ser302 in rat/mouse IRS-1 (corresponding to Ser307 of human IRS-1) is phosphorylated rapidly during insulin stimulation and has a postive role in IRS-1 tyrosine phosphorylation. Inhibition of Ser302 phosphorylation by short-term amino acid/glucose starvation correlates with a decrease in IRS-1 tyrosine phosphorylation without inhibition of insulin receptor autophosphorylation or Akt phosphorylation. A defect in this positive regulatory pathway may be a mechanism contributing to insulin resistence (11).

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. White, M. F. et al. (2004) J. Biol. Chem. 279, 3447-3454.

注意事项：

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