DUSP16/MKP7 (D5F4) Rabbit mAb

• 产品编号：CST-5523S      品牌：CST       原厂货号：5523S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

DUSP16/MKP7 (D5F4)Rabbit mAb兔单抗可以识别内源性总的DUSP16蛋白。单克隆抗体由合成肽段免疫动物产生，该肽段与人DUSP16蛋白Lys431附近氨基酸一致。MAPK能被双特异性蛋白磷酸酶（DUSPs）失活，DUSPs由其不同的底物、组织分布、细胞外刺激的诱导性和细胞内定位而不同。DUSPs，也被称为MAPK磷酸酶（MKP），能够特异性的去磷酸化MAPK P-loops的苏氨酸和酪氨酸残基，在调控MAPK家族功能的过程中发挥了重要作用（1,2）。已经发现了至少13个成员(DUSP1-10, DUSP14, DUSP16和DUSP22)，针对多种MAPK展现了独特的底物特异性（3）。MAPK磷酸酶含有典型的氨基端rhodanese-fold以便DUSP与MAPK家族成员结合，和一个羧基端催化结构域（4）。这些磷酸酶在发育、免疫系统功能、压力应激和代谢稳态过程中发挥了重要作用（5）。此外，研究提示DUSPs涉及了癌症发展和癌细胞对化疗的反应（6）。DUSP16/MKP7是压力激活MAP激酶JNK/SAPK 家族的负调因子。它能通过去磷酸化JNK蛋白活化环中的苏氨酸和酪氨酸残基以抑制JNK信号通路，以及进一步地抑制下游效应分子（7,8）。氧化应激后DUSP16/MKP7会表达上调，这被认为是一种抑制JNK活性以保证细胞回到稳态的方式（9）。大多数细胞中DUSP16都会发生翻转，但是钙蛋白的稳定性能够在通过Erk1/2介导的Ser446磷酸化被加强，这表明有丝分裂原信号通路可通过维持JNK磷酸酶的稳定性以抑制压力应激通路（10,11）。尽管已经证明DUSP16/MKP7对于JNK蛋白有底物偏好性，也有结果表明DUSP16/MKP7可以和其他的MAPK家族成员(Erk1/2, p38 MAPKs)以及一些可能参与其活性和特异性的支架蛋白结合（12,13）。 DUSP15在Burkitt's lymphoma中会通过增加5‘调控区域的甲基化而被表观遗传学的沉默（14）。DUSP16基因的甲基化和DUSP16蛋白的表达是被基础JNK活性相反的进行调控的，提示DUSP16/MKP7维持正常细胞JNK信号通路处于“关闭”状态（14）。最近发现，DUSP16/MKP7在T helper（Th）细胞分化为Th1和Th2细胞的过程中，通过介导JNK信号通路发挥了重要作用（15）。DUSP16/MKP7在Th2细胞中高表达，在Th1细胞中低表达，导致JNK活性的低（Th2）或高（Th1）。这提示DUSP16的表达是Th细胞平衡的一个调控因素（15）。

1. Camps, M. et al. (2000) FASEB J 14, 6-16.
2. Theodosiou, A. and Ashworth, A. (2002) Genome Biol 3, REVIEWS3009.
3. Salojin, K. and Oravecz, T. (2007) J Leukoc Biol 81, 860-9.
4. Tanoue, T. et al. (2002) J Biol Chem 277, 22942-9.
5. Dickinson, R.J. and Keyse, S.M. (2006) J Cell Sci 119, 4607-15.
6. Wu, G.S. (2007) Cancer Metastasis Rev 26, 579-85.
7. Matsuguchi, T. et al. (2001) Mol Cell Biol 21, 6999-7009.
8. Masuda, K. et al. (2001) J Biol Chem 276, 39002-11.
9. Teng, C.H. et al. (2007) J Biol Chem 282, 28395-407.
10. Katagiri, C. et al. (2005) J Biol Chem 280, 14716-22.
11. Masuda, K. et al. (2003) J Biol Chem 278, 32448-56.
12. Willoughby, E.A. and Collins, M.K. (2005) J Biol Chem 280, 25651-8.
13. Willoughby, E.A. et al. (2003) J Biol Chem 278, 10731-6.
14. Lee, S. et al. (2010) Br J Cancer 103, 265-74.
15. Musikacharoen, T. et al. (2011) J Biol Chem 286, 24896-905.

原厂资料：

Homology

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

Specificity / Sensitivity

DUSP16/MKP7 (D5F4) Rabbit mAb recognizes endogenous levels of total DUSP16 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Lys431 of human DUSP16 protein.

Background

MAP kinases are inactivated by dual-specificity protein phosphatases (DUSPs) that differ in their substrate specificity, tissue distribution, inducibility by extracellular stimuli, and cellular localization. DUSPs, also known as MAPK phosphatases (MKP), specifically dephosphorylate both threonine and tyrosine residues in MAPK P-loops and have been shown to play important roles in regulating the function of the MAPK family (1,2). At least 13 members of the family (DUSP1-10, DUSP14, DUSP16, and DUSP22) display unique substrate specificities for various MAP kinases (3). MAPK phosphatases typically contain an amino-terminal rhodanese-fold responsible for DUSP docking to MAPK family members and a carboxy-terminal catalytic domain (4). These phosphatases can play important roles in development, immune system function, stress responses, and metabolic homeostasis (5). In addition, research studies have implicated DUSPs in the development of cancer and the response of cancer cells to chemotherapy (6).DUSP16/MKP7 is a negative regulator of the JNK/SAPK family of stress-activated MAP kinases. It inhibits JNK-mediated signaling events by dephosphorylating threonine and tyrosine residues within the activation loop of JNK proteins, effectively preventing further activation of downstream effectors (7,8). DUSP16/MKP7 expression has been shown to be upregulated after oxidative stress, presumably as a means of supressing JNK activity in order to return the cells to a homeostatic state (9). DUSP16 is normally turned over at a high-rate in most cells, but the stability of the protein can be enhanced by Erk1/2-mediated phosphorylation on Ser446, indicating that activation of mitogenic signaling pathways can supress stress-response pathways via stabilization of a JNK phosphatase (10,11). Despite demonstrating a substrate preference towards JNK proteins, DUSP16/MKP7 has been shown to interact with other MAPK family members (Erk1/2, p38 MAPKs) as well as scaffolding proteins that may coordinate its activity and specificity (12,13). 
 
 DUSP16 is epigenetically silenced in Burkitt's lymphoma by increased methylation of the 5' regulatory regions of the gene (14). Methylation of the DUSP16 gene and expression of DUSP16 protein inversely correlate with increased basal levels of JNK acitvitiy, suggesting DUSP16/MKP7 may play a critical role in maintaining JNK signaling in an "off" state in normal cells (14). More recently, DUSP16/MKP7 has been shown to play a crucial role in T helper (Th) cell differentiation into Th1 and Th2 cells, mediated by JNK signaling pathways (15). DUSP16/MKP7 expression is preferentially high in Th2 cells and low in Th1 cells during differentiation, resulting in either low (Th2) or high (Th1) JNK activity. This suggests that DUSP16 expression may be a regulator of Th cell balance (15).

1. Camps, M. et al. (2000) FASEB J 14, 6-16.
2. Theodosiou, A. and Ashworth, A. (2002) Genome Biol 3, REVIEWS3009.
3. Salojin, K. and Oravecz, T. (2007) J Leukoc Biol 81, 860-9.
4. Tanoue, T. et al. (2002) J Biol Chem 277, 22942-9.
5. Dickinson, R.J. and Keyse, S.M. (2006) J Cell Sci 119, 4607-15.
6. Wu, G.S. (2007) Cancer Metastasis Rev 26, 579-85.
7. Matsuguchi, T. et al. (2001) Mol Cell Biol 21, 6999-7009.
8. Masuda, K. et al. (2001) J Biol Chem 276, 39002-11.
9. Teng, C.H. et al. (2007) J Biol Chem 282, 28395-407.
10. Katagiri, C. et al. (2005) J Biol Chem 280, 14716-22.
11. Masuda, K. et al. (2003) J Biol Chem 278, 32448-56.
12. Willoughby, E.A. and Collins, M.K. (2005) J Biol Chem 280, 25651-8.
13. Willoughby, E.A. et al. (2003) J Biol Chem 278, 10731-6.
14. Lee, S. et al. (2010) Br J Cancer 103, 265-74.
15. Musikacharoen, T. et al. (2011) J Biol Chem 286, 24896-905.

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.