Phospho-KSR1 (Ser392) Antibody

• 产品编号：CST-4951S      品牌：CST       原厂货号：4951S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-KSR1 (Ser392) Antibody兔多抗能检测内源性丝氨酸（392位点）磷酸化的KSR1蛋白水平。该抗体也许能与相同位点磷酸化的KSR2蛋白发生交叉反应。该多克隆抗体是通过用与人源KSR1蛋白丝氨酸（392位点）周围残基相一致的磷酸化的合成肽段免疫动物后获得的。该抗体经蛋白A和肽亲和层析纯化。KSR1（Ras激酶抑制子）在Drosophila和C. Elegans的遗传筛选中被发现，它是Ras信号传递途径的组成部分(1)。KSR1有一个假定的羧端激酶结构域，该结构域缺乏含磷基团转移所需的核心赖氨酸残基。尽管有报道称神经酰胺和EGF能激活KSR1 (2,3)，但是其他证据表明KSR1以激酶依赖形式调节Raf蛋白(4,5)。人们普遍认为KSR1作为支架蛋白结构性连接MEK1/2、14-3-3蛋白，并以Ras活化依赖型方式结合ERK1/2(1,5,6)。HSP70/HSP90和p50 Cdc37与KSR1相关，能确保它的稳定性(5)。目前已经证实了许多磷酸化位点：丝氨酸（297、274位点）介导14-3-3蛋白结合，以及假定的MAPK磷酸化位点包括苏氨酸（260、274位点），丝氨酸（443位点）(6)。在静止期细胞中，C-TAK1 (Cdc25C-相关激酶1)结合并磷酸化KSR1丝氨酸（392位点）(7)。对外界刺激做出应答后丝氨酸（392位点）就被PP2A蛋白去磷酸化，导致与ERK1/2联合并使KSR1复合物从胞质转移到胞膜，激活MAPK途径(8)。IMP，Ras应答的E3泛素连接酶，也参与KSR1的相互作用，并调节它的定位和稳定性(9)。KSR1的高水平表达抑制了MAPK的信号传递，然而在生理学水平却促进了MAPK的信号传递，这种现象表明依赖支架蛋白的浓度，支架蛋白能“开启”或“关闭”信号的传导(10)。

1. Morrison, D.K. (2001) J. Cell Sci. 114, 1609-1612.
2. Zhang, Y. et al. (1997) Cell 89, 63-72.
3. Xing, H.R. and Kolesnick, R. (2001) J. Biol. Chem. 276, 9733-9741.
4. Michaud, N. R. et al. (1997) Proc. Natl. Acad. Sci. USA 94, 12792-12796.
5. Stewart, S. et al. (1999) Mol. Cell. Biol. 19, 5523-5534.
6. Muller, J. et al. (2001) Mol. Cell 8, 983-993.
7. Cacace, A. M. et al. (1999) Mol. Cell. Biol. 19, 229-240.
8. Ory, S. et al. (2003) Curr. Biol. 13, 1356-1364.
9. Matheny, S. A. et al. (2004) Nature 427, 256-260.
10. Kortum, R.L. and Lewis, R.E. (2004) Mol Cell Biol 24, 4407-16.

原厂资料：

Specificity / Sensitivity

Phospho-KSR1 (Ser392) Antibody detects endogenous levels of KSR1 only when phosphorylated at serine 392. This antibody may also react with phosphorylated KSR2 at the equivalent site.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser392 of mouse KSR1. Antibodies are purified by protein A and peptide affinity chromatography.

Background

KSR1 (kinase supressor of Ras) was identified from a genetic screen in Drosophila and C. elegans as a component of the Ras signaling pathway (1). KSR1 has a putative carboxy-terminal kinase domain that lacks a key Lys residue for phospho-group transfer. Although reports indicate that ceramide and EGF activate KSR1 (2,3), other evidence demonstrates that KSR1 regulates Raf in a kinase-independent manner (4,5). It is now widely accepted that KSR1 functions as a scaffold that binds MEK1/2 and 14-3-3 protein constitutively and binds ERK1/2 in a Ras activation-dependent manner (1,5,6). HSP70/HSP90 and p50 Cdc37 associate with the KSR1 complex to ensure its stability (5). Multiple phosphorylation sites have been identified: Ser297 and Ser392 mediate 14-3-3 binding, and putative MAPK phosphorylation sites include Thr260, Thr274 and Ser443 (6). C-TAK1 (Cdc25C-associated kinase 1) binds and phosphorylates KSR1 at Ser392 in quiescent cells (7). In response to stimuli, Ser392 is dephosphorylated by PP2A, which leads to ERK1/2 association and allows the KSR1 complex to translocate from cytosol to membrane, where the MAPK pathway is activated (8). IMP, a Ras-responsive E3 ubiquitin ligase, is also involved in interaction with KSR1 and may regulate its localization and stability (9). Very high expression levels of KSR1 inhibit MAPK signaling, whereas physiological levels promote MAPK signaling, indicating that the scaffold protein can turn signaling "on" or "off" depending on the scaffold concentration (10).

1. Morrison, D.K. (2001) J. Cell Sci. 114, 1609-1612.
2. Zhang, Y. et al. (1997) Cell 89, 63-72.
3. Xing, H.R. and Kolesnick, R. (2001) J. Biol. Chem. 276, 9733-9741.
4. Michaud, N. R. et al. (1997) Proc. Natl. Acad. Sci. USA 94, 12792-12796.
5. Stewart, S. et al. (1999) Mol. Cell. Biol. 19, 5523-5534.
6. Muller, J. et al. (2001) Mol. Cell 8, 983-993.
7. Cacace, A. M. et al. (1999) Mol. Cell. Biol. 19, 229-240.
8. Ory, S. et al. (2003) Curr. Biol. 13, 1356-1364.
9. Matheny, S. A. et al. (2004) Nature 427, 256-260.
10. Kortum, R.L. and Lewis, R.E. (2004) Mol Cell Biol 24, 4407-16.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody