Phospho-p90RSK (Thr359) (D1E9) Rabbit mAb

• 产品编号：CST-8753S      品牌：CST       原厂货号：8753S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-p90RSK (Thr359) (D1E9) Rabbit mAb兔单抗可以识别内源性的Thr359被磷酸化的p90RSK1蛋白。此抗体也能识别Thr365被磷酸化的p90RSK2和Thr356被磷酸化的p90RSK3。p90RSK亚型丝氨酸残基的磷酸化(Ser363 of p90RSK1, Ser369 of p90RSK2, 和Ser360 of p90RSK3)并不影响该抗体对磷酸化苏氨酸残基的检测。该单克隆抗体由合成肽段免疫动物产生，该肽段与人p90RSK3蛋白Thr356附近氨基酸一致。90kDa核糖体S6激酶(RSK1-4)是一个广泛表达的丝/苏氨酸激酶家族，其特征是包含2个不同的功能性激酶结构域（1）和一个羧基端的细胞外信号调节激酶（ERKs）结合位点（2）。RSK激酶结构域内或以外的一些位点，包括Ser380, Thr359, Ser363和Thr573，对于激酶的激活非常重要（3）。RSK1-3在多种生长因子、多肽激素和神经递质的刺激下，通过MAPKs的磷酸化作用、自磷酸化作用以及PI3K的信号途径的协同作用被激活（3）。在有丝分裂原的刺激下，p44/42 Erk1/2和Erk5 MAPK能够协同磷酸化p90RSK位于C末端激酶结构域的Thr573 (p90RSK1 numbering)以及位于两个激酶结构域间链接序列的Thr359/Ser363 (3)。p90RSK C末端激酶结构域活化环内Thr573位点的磷酸化能够促进连接区域疏水区内的Ser380位点的磷酸化及活化过程（4,5）。被磷酸化后，Ser380能够作为组成型活化的Ser/Thr激酶PDK1的结合位点，随后使p90RSK的N末端激酶结构活化环内的Ser221位点被磷酸化，导致p90RSK酶活性的全面激活（6）。针对这些磷酸化位点的抗体对于理解p90RSK活性的动力学原理和调控是有用的。为了获得更多每个RSK亚型磷酸化位点的信息，包括证明这些复合物磷酸化所涉及的级联反应，请参考参考文献和PhosphoSitePlus® (www.phosphosite.org)。

1. Fisher, T.L. and Blenis, J. (1996) Mol Cell Biol 16, 1212-9.
2. Smith, J.A. et al. (1999) J Biol Chem 274, 2893-8.
3. Dalby, K.N. et al. (1998) J Biol Chem 273, 1496-505.
4. Roux, P.P. et al. (2003) Mol Cell Biol 23, 4796-804.
5. Cargnello, M. and Roux, P.P. (2011) Microbiol Mol Biol Rev 75, 50-83.
6. Romeo, Y. et al. (2012) Biochem J 441, 553-69.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Chicken, Xenopus, Dog, Horse

Specificity / Sensitivity

Phospho-p90RSK (Thr359) (D1E9) Rabbit mAb recognizes endogenous levels of p90RSK1 protein when phosphorylated at Thr359. This antibody also detects p90RSK2 phosphorylated at Thr365 and p90RSK3 phosphorylated at Thr356. Phosphorylation of p90RSK isoforms at a proximal serine residue (Ser363 of p90RSK1, Ser369 of p90RSK2, and Ser360 of p90RSK3) does not affect the ability of this antibody to detect the phospho-Thr residue.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Thr356 of human p90RSK3 protein.

Background

The 90 kDa ribosomal S6 kinases (RSK1-4) are a family of widely expressed Ser/Thr kinases characterized by two nonidentical, functional kinase domains (1) and a carboxy-terminal docking site for extracellular signal-regulated kinases (ERKs) (2). Several sites both within and outside of the RSK kinase domain, including Ser380, Thr359, Ser363, and Thr573, are important for kinase activation (3). RSK1-3 are activated via coordinated phosphorylation by MAPKs, autophosphorylation, and phosphoinositide-3-OH kinase (PI3K) in response to many growth factors, polypeptide hormones, and neurotransmitters (3).Upon mitogenic stimulation, p44/42 Erk1/2 and Erk5 MAP kinases cooperatively phosphorylate p90RSK at Thr573 (p90RSK1 numbering) located within the C-terminal kinase domain and at Thr359/Ser363 in the linker region between the two kinase domains (3). Phosphorylation at Thr573 within the activation loop of the p90RSK C-terminal kinase domain promotes activation and directs phosphorylation at Ser380 within the hydrophobic stretch of the linker region (4,5). When phosphorylated, Ser380 acts as a docking site for the constitutively active Ser/Thr kinase PDK1, which in turn phosphorylates p90RSK at Ser221 within the N-terminal kinase domain activation loop, resulting in full enzymatic activation of p90RSK (6). Antibodies against these phosphorylation sites are useful for understanding the kinetics and regulation of p90RSK activation. 
 For more information regarding the phospho-regulatory sites within each RSK isoform, including more information regarding the seminal studies demonstrating the complex phosphorylation cascades involved, please see the references herein and PhosphoSitePlus® (www.phosphosite.org).

1. Fisher, T.L. and Blenis, J. (1996) Mol Cell Biol 16, 1212-9.
2. Smith, J.A. et al. (1999) J Biol Chem 274, 2893-8.
3. Dalby, K.N. et al. (1998) J Biol Chem 273, 1496-505.
4. Roux, P.P. et al. (2003) Mol Cell Biol 23, 4796-804.
5. Cargnello, M. and Roux, P.P. (2011) Microbiol Mol Biol Rev 75, 50-83.
6. Romeo, Y. et al. (2012) Biochem J 441, 553-69.

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