Phospho-FRA1 (Ser265) (D22B1) Rabbit mAb

• 产品编号：CST-5841P      品牌：Cell Signaling Technology       原厂货号：5841P
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-FRA1 (Ser265) (D22B1) Rabbit mAb兔单抗能识别内源性Ser265位点磷酸化的FRA1蛋白水平。该抗体可能会与其他phospho-FRA2 蛋白发生交叉反应，但是不与phospho-c-Fos 、 phospho-FosB蛋白发生交叉反应。该单克隆抗体通过使用与人源 FRA1 蛋白Ser265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。细胞核原癌基因的Fos家族成员包括c-Fos、FosB、Fos-相关抗原1 (FRA1)、Fos-相关抗原2 (FRA2)。虽然大部分Fos蛋白以单一亚型存在，但是FosB蛋白以两种亚型存在：全长的FosB蛋白和缩短的形式——FosB2 (Delta FosB)，后者缺乏羧端的101个氨基酸(1-3)。Fos蛋白的表达是由细胞外刺激子快速且瞬间诱导的，这些刺激因子包括生长因子、细胞因子、神经传导物质、多肽激素和应激反应。Fos蛋白和Jun蛋白(c-Jun, JunB, 和JunD)结合成二聚体形成活化因子蛋白-1 (AP-1)，它是结合到TRE/AP-1元件上的转录因子，并且能激活转录。Fos、Jun蛋白包含一个亮氨酸拉链基序，能调节二聚化和结合DNA的一个毗邻碱性域。各种Fos/Jun二聚体的不同点在于反式激活AP-1依赖性基因的能力。Fos蛋白对细胞外刺激因子应答后，除了表达量增加，同时也被Erk蛋白磷酸化，它的磷酸化可能会进一步增强转录活性(4-6)。Erk5蛋白引起的c-Fos蛋白Ser32位点和Thr232位点的磷酸化增强了蛋白质稳定性和核定位(5)。Erk1/2引起的FRA1蛋白Ser252、Ser265位点的磷酸化增强了蛋白稳定性，导致癌细胞内FRA1蛋白的过量表达(6)。生长因子刺激后，相对静止的成纤维细胞中FosB、c-Fos蛋白表达在短时间内被激活，但是几个小时后就消失了(7)。FRA1、 FRA2的表达持续时间更长，而且在异步生长细胞中能检测到它(8)。c-Fos, FosB, 和FRA2的失控表达将导致细胞的癌变；然而Delta FosB蛋白能阻止这种细胞转化的能力(2,3)。

1. Tulchinsky, E. (2000) Histol Histopathol 15, 921-8.
2. Dobrazanski, P. et al. (1991) Mol Cell Biol 11, 5470-8.
3. Nakabeppu, Y. and Nathans, D. (1991) Cell 64, 751-9.
4. Rosenberger, S.F. et al. (1999) J Biol Chem 274, 1124-30.
5. Sasaki, T. et al. (2006) Mol Cell 24, 63-75.
6. Basbous, J. et al. (2007) Mol Cell Biol 27, 3936-50.
7. Kovary, K. and Bravo, R. (1991) Mol Cell Biol 11, 2451-9.
8. Kovary, K. and Bravo, R. (1992) Mol Cell Biol 12, 5015-23.

原厂资料：

Homology

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

Specificity / Sensitivity

Phospho-FRA1 (Ser265) (D22B1) Rabbit mAb recognizes endogenous levels of FRA1 protein only when phosphorylated at Ser265. This antibody may also cross-react with phospho-FRA2, but does not cross-react with phospho-c-Fos or phospho-FosB.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser265 of human FRA1 protein.

Background

The Fos family of nuclear oncogenes includes c-Fos, FosB, Fos-related antigen 1 (FRA1), and Fos-related antigen 2 (FRA2) (1). While most Fos proteins exist as a single isoform, the FosB protein exists as two isoforms: full-length FosB and a shorter form, FosB2 (Delta FosB), that lacks the carboxy-terminal 101 amino acids (1-3). The expression of Fos proteins is rapidly and transiently induced by a variety of extracellular stimuli including growth factors, cytokines, neurotransmitters, polypeptide hormones, and stress. Fos proteins dimerize with Jun proteins (c-Jun, JunB, and JunD) to form Activator Protein-1 (AP-1), a transcription factor that binds to TRE/AP-1 elements and activates transcription. Fos and Jun proteins contain the leucine-zipper motif that mediates dimerization and an adjacent basic domain that binds to DNA. The various Fos/Jun heterodimers differ in their ability to transactivate AP-1 dependent genes. In addition to increased expression, phosphorylation of Fos proteins by Erk kinases in response to extracellular stimuli may further increase transcriptional activity (4-6). Phosphorylation of c-Fos at Ser32 and Thr232 by Erk5 increases protein stability and nuclear localization (5). Phosphorylation of FRA1 at Ser252 and Ser265 by Erk1/2 increases protein stability and leads to overexpression of FRA1 in cancer cells (6). Following growth factor stimulation, expression of FosB and c-Fos in quiescent fibroblasts is immediate, but very short-lived, with protein levels dissipating after several hours (7). FRA1 and FRA2 expression persists longer and appreciable levels can be detected in asynchronously growing cells (8). Deregulated expression of c-Fos, FosB, or FRA2 can result in neoplastic cellular transformation; however, Delta FosB lacks the ability to transform cells (2,3).

1. Tulchinsky, E. (2000) Histol Histopathol 15, 921-8.
2. Dobrazanski, P. et al. (1991) Mol Cell Biol 11, 5470-8.
3. Nakabeppu, Y. and Nathans, D. (1991) Cell 64, 751-9.
4. Rosenberger, S.F. et al. (1999) J Biol Chem 274, 1124-30.
5. Sasaki, T. et al. (2006) Mol Cell 24, 63-75.
6. Basbous, J. et al. (2007) Mol Cell Biol 27, 3936-50.
7. Kovary, K. and Bravo, R. (1991) Mol Cell Biol 11, 2451-9.
8. Kovary, K. and Bravo, R. (1992) Mol Cell Biol 12, 5015-23.

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