PD98059

• 产品编号：CST-9900L      品牌：CST       原厂货号：9900L
• 产品分类：生化试剂 > 生物试剂 > 生物活性小分子 > 抑制剂
• 应用分类：

描述：

PD98059 (MEK1抑制剂)在10-100 mM时能溶于DMSO。它能用于体内和细胞水平研究，也许能在水相缓冲液中被稀释成理想的浓度(<100 µM)，DMSO中的终浓度为 ~0.1%。抑制MEK1蛋白的活性值IC50在5-10 µM左右。对于实验中培养的细胞，CTS建议先用该抑制子处理1h，在进行刺激。MEK1、MEK2,也被称为MAPK或Erk激酶，它们是双特异性蛋白激酶，在丝裂原活化蛋白激酶级联反应中发挥作用，控制细胞生长和分化(1-3)。MEK1、MEK2的活化是通过Raf样分子对两个丝氨酸（217 /221位点）的磷酸化而实现的，这两个丝氨酸位点位于亚结构域VIII的活化环内。多种生长因子和细胞因子以及膜去极化和钙内流都能激活MEK1/2(1-4)。组成型活化的MEK1/2能够诱导NIH/3T3细胞的转化和PC-12细胞的分化(4)。MEK蛋白通过将p44、p42 MAPK激酶上位于亚结构域VIII的活化环内的丝氨酸和苏氨酸磷酸化，激活p44、 p42 MAPK激酶。已经证明体内的PD98059 (MEK1 抑制子)是MEK1 活化和MAP激酶级联反应的高选择性抑制子(1-4)。PD98059结合MEK1的非活化形式，并阻止上游活化因子如c-Raf的活化作用 (3)。

1. Crews, C.M. et al. (1992) Science 258, 478-80.
2. Alessi, D.R. et al. (1994) EMBO J 13, 1610-9.
3. Rosen, L.B. et al. (1994) Neuron 12, 1207-21.
4. Cowley, S. et al. (1994) Cell 77, 841-52.

原厂资料：

Description

PD98059 (MEK1 Inhibitor) is soluble in DMSO at 10-100 mM. For use with in vitro or cell-based assays, it may be diluted into aqueous buffers to yield desired concentrations (<100 µM) with final DMSO concentrations of ~0.1%. IC50 values for inhibitory activity against MEK1 are around 5-10 µM. For experiments with cultured cells, CST recommends pretreating with this inhibitor for one hour prior to stimulation.

Directions for Use

Supplied as a lyophilized yellow powder. For 20 mM stock, reconstitute 1.5 mg in 280 µl DMSO (5 mg in 933.3 μl). For 50 mM stock, reconstitute 1.5 mg in 112 µl DMSO (5 mg in 373.3 μl). Store in aliquots at -20ºC. See enclosed MSDS for further information. This product is for in vitro research use only and is not intended for use in humans or animals.

Background

MEK1 and MEK2, also called MAPK or Erk kinases, are dual-specificity protein kinases that function in a mitogen activated protein kinase cascade controlling cell growth and differentiation (1-3). Activation of MEK1 and MEK2 occurs through phosphorylation of two serine residues at positions 217 and 221, located in the activation loop of subdomain VIII, by Raf-like molecules. MEK1/2 is activated by a wide variety of growth factors and cytokines and also by membrane depolarization and calcium influx (1-4). Constitutively active forms of MEK1/2 are sufficient for the transformation of NIH/3T3 cells or the differentiation of PC-12 cells (4). MEK activates p44 and p42 MAP kinase by phosphorylating both threonine and tyrosine residues at sites located within the activation loop of kinase subdomain VIII.PD98059 (MEK1 Inhibitor) has been shown to act in vivo as a highly selective inhibitor of MEK1 activation and the MAP kinase cascade (1-4). PD98059 binds to the inactive forms of MEK1 and prevents activation by upstream activators such as c-Raf (3).

1. Crews, C.M. et al. (1992) Science 258, 478-80.
2. Alessi, D.R. et al. (1994) EMBO J 13, 1610-9.
3. Rosen, L.B. et al. (1994) Neuron 12, 1207-21.
4. Cowley, S. et al. (1994) Cell 77, 841-52.

注意事项：

Storage: Store lyophilized or in solution at -20ºC, desiccated.
In lyophilized form, the chemical is stable for 24 months. Once
in solution, use within 3 months to prevent loss of potency.
Aliquot to avoid multiple freeze/thaw cycles.