MEKK3 (D36G5) Rabbit mAb

• 产品编号：CST-5727S      品牌：CST       原厂货号：5727S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

MEKK3 (D36G5) Rabbit mAb兔单抗能识别内源性总MEKK3蛋白水平。该单克隆抗体通过使用与人源MEKK3蛋白氨脯氨酸（310位点）周围残基相一致的磷酸化的合成肽段免疫动物而获得。MAP kinase kinase kinase (MEKK3 or MAP3K3)是一种丝氨酸/苏氨酸蛋白激酶，它能激活SAPK and ERK，通过它们各自MAP激酶的激酶——SEK and MEK1/2的磷酸化和活化。MEKK3也能经ERK5/BMK1的活化而刺激MEK5，这一反应过程至少有一部分是由MEK5与MEKK3的直接相互作用调节的。MEK5与MEKK3的相互作用通过这两种蛋白的p67phox-Bem1p (PB1)蛋白与蛋白相互作用区域实现的(3,4)。MEKK3调节NF-κB的活性，以应答各种激动剂的效应，包括NFα, LPS, IL-1、LPA (5-9)。尽管有报道称MEKK3活化环内丝氨酸（526位点）的磷酸化是激酶活化必须的(10-12)，但是至少有一个研究暗示苏氨酸（294位点）和丝氨酸（520位点）是 LPA-s刺激的IKKβ/NF-κB活化所必需的(13)。苏氨酸（294位点）的磷酸化促进了14-3-3β的结合并抑制了激酶活性，从而导致MEKK3的负调节作用(12)。LPS、TNFα 处理细胞后，MEKK3苏氨酸（294位点）的磷酸化被削弱，进一步暗示了它对该位点的抑制作用(12)。

1. Blank, J.L. et al. (1996) J Biol Chem 271, 5361-8.
2. Ellinger-Ziegelbauer, H. et al. (1997) J Biol Chem 272, 2668-74.
3. Nakamura, K. and Johnson, G.L. (2003) J Biol Chem 278, 36989-92.
4. Nakamura, K. et al. (2010) J Biol Chem 285, 2077-89.
5. Yang, J. et al. (2001) Nat Immunol 2, 620-4.
6. Zhao, Q. and Lee, F.S. (1999) J Biol Chem 274, 8355-8.
7. Samanta, A.K. et al. (2004) J Biol Chem 279, 7576-83.
8. Huang, Q. et al. (2004) Nat Immunol 5, 98-103.
9. Sun, W. et al. (2009) Cell Signal 21, 1488-94.
10. Zhang, D. et al. (2006) EMBO J 25, 97-107.
11. Fritz, A. et al. (2006) J Biol Chem 281, 6236-45.
12. Matitau, A.E. and Scheid, M.P. (2008) J Biol Chem 283, 13261-8.
13. Sun, W. et al. (2010) J Biol Chem 285, 7911-18.

原厂资料：

Specificity / Sensitivity

MEKK3 (D36G5) Rabbit mAb recognizes endogenous levels of total MEKK3 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro310 of human MEKK3 protein.

Background

MAP kinase kinase kinase (MEKK3 or MAP3K3) is a serine/threonine protein kinase that activates SAPK and ERK via phosphorylation and activation of their respective MAP kinase kinases, SEK and MEK1/2 (1,2). MEKK3 also stimulates MEK5 via activation of ERK5/BMK1, which is at least partly regulated by a direct interaction between MEK5 and MEKK3 via p67phox-Bem1p (PB1) protein-protein interaction domains found in both proteins (3,4). MEKK3 modulates NF-κB activation in response to a variety of agonists including TNFα, LPS, IL-1 and LPA (5-9). Despite reports showing that phosphorylation of MEKK3 at Ser526 within the activation loop is necessary for kinase activation (10-12), at least one study suggests that dual phosphorylation at Thr516 and Ser520 is required for LPA-stimulated IKKβ/NF-κB activation (13). Phosphorylation at Thr294 appears to negatively regulate MEKK3 by promoting 14-3-3β binding and inhibition of the kinase activity (12). Phosphorylation of MEKK3 at Thr294 is diminished upon treatment of cells with LPS or TNFα, further suggesting an inhibitory role for this site (12).

1. Blank, J.L. et al. (1996) J Biol Chem 271, 5361-8.
2. Ellinger-Ziegelbauer, H. et al. (1997) J Biol Chem 272, 2668-74.
3. Nakamura, K. and Johnson, G.L. (2003) J Biol Chem 278, 36989-92.
4. Nakamura, K. et al. (2010) J Biol Chem 285, 2077-89.
5. Yang, J. et al. (2001) Nat Immunol 2, 620-4.
6. Zhao, Q. and Lee, F.S. (1999) J Biol Chem 274, 8355-8.
7. Samanta, A.K. et al. (2004) J Biol Chem 279, 7576-83.
8. Huang, Q. et al. (2004) Nat Immunol 5, 98-103.
9. Sun, W. et al. (2009) Cell Signal 21, 1488-94.
10. Zhang, D. et al. (2006) EMBO J 25, 97-107.
11. Fritz, A. et al. (2006) J Biol Chem 281, 6236-45.
12. Matitau, A.E. and Scheid, M.P. (2008) J Biol Chem 283, 13261-8.
13. Sun, W. et al. (2010) J Biol Chem 285, 7911-18.

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.