JIP4/SPAG9 (D72F4) XP? Rabbit mAb

• 产品编号：CST-5519S      品牌：CST       原厂货号：5519S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

JIP4/SPAG9 (D72F4) XP® Rabbit mAb兔单抗能识别内源性总JIP4蛋白的水平。该抗体能检测已知的JIP4剪切异构体 (SPAG9, JLP)，但是不能确定它是不是会与其他JIP家族成员发生交叉反应。该单克隆抗体通过使用与人源JIP4蛋白亮氨酸（237位点）周围区域残基相一致的合成肽段免疫动物而获得。JNK-Interacting Proteins (JIPs)顾名思义，通过充当JNK信号传导级联组成的支架蛋白，而调节 c-JunN-末端激酶（JNK）的信号转导(1)。 JIPs使JNK局部化并促进JNK的活化，通过合并以及共局部化上游激酶和下游效应子应答应激反应，这种应激——激酶途径类似于AKAPs协调PKA信号转导的机制。JIPs结合MAPKs的序列以及其他信号转导蛋白，包括混合激酶， MKK7, p38α MAPK, JNK1-3, Max, Myc, NF-κB, LRRK2等 (1-4)。目前已知四个 JIPs, JIP1-4, ，其中JIP1 、JIP2共有大量的同源序列和域结构。JIP1 、JIP2主要表达于神经元、睾丸以及β胰腺细胞中，它们涉及对代谢应激、糖尿病发展和创伤后大脑损伤作出的细胞应答反应 (5-7)。尽管在结构上与JIP1、JIP2不同，, JIP3 、JIP4 共享一些重叠作用，并更加广泛地表达。JIP4由SPAG9 (sperm-associated antigen-9) 基因编码，是一个同源寡聚体，能结合并协调许多应激活化激酶级联成分的活化，包括MEK4, MEKK3, p38α MAPK, 和JNK1-3 (3,8)。然而，不像其他JIP成员，JIP4不能直接活化JNK，而更倾向于在应答应激反应后，刺激p38 MAPK的信号转导 (3,9)。除了调节压力效应，JIP4（或它的剪切异构体JLP）也能与 ARF6 and PIKfyve相互作用，因此调节微管的内涵体运输 (10,11)。大量报道表明JIP4应答应激反应（紫外损失等）后，被磷酸化，但是不清楚会产生什么效果，如果有的话，是对它的作用、位置或结合特性产生的影响(12-15)。

1. Jagadish, N. et al. (2005) Biochem J 389, 73-82.
2. Bouwmeester, T. et al. (2004) Nat Cell Biol 6, 97-105.
3. Kelkar, N. et al. (2005) Mol Cell Biol 25, 2733-43.
4. Hsu, C.H. et al. (2010) Neurodegener Dis 7, 68-75.
5. Willoughby, E.A. et al. (2003) J Biol Chem 278, 10731-6.
6. Koushika, S.P. (2008) Bioessays 30, 10-4.
7. Beeler, N. et al. (2009) Brain Res Bull 80, 274-81.
8. Brancho, D. et al. (2003) Genes Dev 17, 1969-78.
9. Ikonomov, O.C. et al. (2009) J Biol Chem 284, 3750-61.
10. Montagnac, G. et al. (2009) Curr Biol 19, 184-95.
11. Olsen, J.V. et al. (2006) Cell 127, 635-48.
12. Molina, H. et al. (2007) Proc Natl Acad Sci U S A 104, 2199-204.
13. Matsuoka, S. et al. (2007) Science 316, 1160-6.
14. Dephoure, N. et al. (2008) Proc Natl Acad Sci U S A 105, 10762-7.

原厂资料：

Specificity / Sensitivity

JIP4/SPAG9 (D72F4) XP® Rabbit mAb recognizes endogenous levels of total JIP4 protein. This antibody will detect known splice variants of JIP4 (SPAG9, JLP) but is not predicted to cross-react with other JIP family members.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to a region surrounding Leu237 of human JIP4 protein.

Background

JNK-Interacting Proteins (JIPs), as their name implies, coordinate c-Jun N-terminal Kinase (JNK) signaling by acting as scaffolds for components of the JNK signaling cascade (1). JIPs localize and promote JNK activation in response to stress by amalgamating and co-localizing upstream kinases and downstream effectors in the stress-kinase pathway analogous to the mechanism by which AKAPs orchestrate PKA signaling. JIPs bind to an array of MAPKs and other signaling proteins, including the mixed-lineage kinases, MKK7, p38α MAPK, JNK1-3, Max, Myc, NF-κB, LRRK2, and others (1-4). 
 
 There are four known JIPs, JIP1-4, of which JIP1 and JIP2 share extensive sequence homology and domain structure. JIP1 and JIP2 are mainly expressed in neurons, testis and in β pancreatic cells, where they have been implicated in cellular responses to metabolic stress, the development of diabetes, and post-traumatic brain damage (5-7). Although architecturally distinct from JIP1 and JIP2, JIP3 and JIP4 share some overlapping functions and are more broadly expressed. JIP4, encoded by the SPAG9 (sperm-associated antigen-9) gene, is a homooligomer that binds to and coordinates the activation of numerous components of the stress-activated kinase cascade including MEK4, MEKK3, p38α MAPK, and JNK1-3 (3,8). However, unlike the other JIP members, JIP4 does not appear to activate JNK directly, instead favoring stimulation of p38 MAPK signaling events in response to cellular stress (3,9). 
 
 In addition to mediating stress responses, JIP4 (or its splice variant, JLP) has also been shown to interact with ARF6 and PIKfyve, thus regulating microtubule-based endosomal trafficking (10,11). There are extensive reports indicating that JIP4 is phosphorylated in response to stress (UV damage etc.) but it is unclear what effect, if any, this has on its function, localization, or binding properties (12-15).

1. Jagadish, N. et al. (2005) Biochem J 389, 73-82.
2. Bouwmeester, T. et al. (2004) Nat Cell Biol 6, 97-105.
3. Kelkar, N. et al. (2005) Mol Cell Biol 25, 2733-43.
4. Hsu, C.H. et al. (2010) Neurodegener Dis 7, 68-75.
5. Willoughby, E.A. et al. (2003) J Biol Chem 278, 10731-6.
6. Koushika, S.P. (2008) Bioessays 30, 10-4.
7. Beeler, N. et al. (2009) Brain Res Bull 80, 274-81.
8. Brancho, D. et al. (2003) Genes Dev 17, 1969-78.
9. Ikonomov, O.C. et al. (2009) J Biol Chem 284, 3750-61.
10. Montagnac, G. et al. (2009) Curr Biol 19, 184-95.
11. Olsen, J.V. et al. (2006) Cell 127, 635-48.
12. Molina, H. et al. (2007) Proc Natl Acad Sci U S A 104, 2199-204.
13. Matsuoka, S. et al. (2007) Science 316, 1160-6.
14. Dephoure, N. et al. (2008) Proc Natl Acad Sci U S A 105, 10762-7.

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.