Jak/Stat Pathway Inhibitors Antibody Sampler Kit

• 产品编号：CST-8343S      品牌：Cell Signaling Technology       原厂货号：8343S
• 产品分类：抗体 > 一抗 > 复合抗体试剂盒
• 应用分类：

其它组分：

描述：

此试剂盒中的每一个抗体都能够识别特异的目标蛋白而且不与其它的家族成员交叉反应。PIAS3，SOCS1，SOCS2，SOCS3的多克隆抗体分别是通过合成人源对应的Thr585，Ala156，C-末端，Leu210位点周围的肽段来免疫动物而获得。抗体是通过protein A和多肽亲和层析法纯化。PIAS1，PIAS4单克隆抗体石是通过合成人源对应的Ser550，Lys59位点周围的肽段来免疫动物而获得。Jak/Stat Pathway Inhibitors Antibody Sampler Kit 为研究Jak/Stat信号通路上多个抑制因子提供了经济的方法，包括PIAS1, PIAS3, PIAS4, SOCS1, SOCS2和SOCS3。本试剂盒内为每个抗体提供了足够四次Western blots 所需的一抗。Jaks (Janus 激酶)和 Stats (转录的信号传感器和激活因子)作为受体能够与多种的配体结合，如细胞因子，激素，生长因子和神经传递素(1)。Jak/Stat信号通路在肿瘤的形成，肿瘤的发展，血管再生术，细胞运动，免疫反应和干细胞分化中起了重要的作用(2-5)。因此，Jak/Stat信号通路的调控对阻止畸变生物信号导致的疾病发展起了重要的作用。两种调控Jak/Stat信号通路方式有SOCS和PIAS蛋白的参与(6,7)。SOCS (抑制因子或细胞因子信号)家族成员是细胞因子信号转导的负调控因子，能够抑制Jak/Stat通路，此家族包含8个已知的成员，包括最初鉴定的蛋白CIS1 (细胞因子诱导的含有SH2的蛋白)和SOCS1-SOCS7。每个SOCS 家族成员包含一个SH2中心域和C-末端域命名为SOCS盒。这些蛋白时细胞因子信号的重要调控者包括细胞增殖、分化和免疫反应(8-10)。SOCS参与调控30多种细胞因子，包括白细胞介素、生长激素(GH)、干扰素、瘦素、和白血病抑制因子(7)。SOCS1, 也叫做JAB (Janus 激酶结合蛋白), SSI-1 (Stat诱导的Stat抑制剂1)，与SOCS3高度同源，并都能够被细胞因子高度诱导(7,11)。SOCS1 和 SOCS3都能够直接的抑制Jak的活性；SOCS1抑制 Jak是通过激酶活性环内磷酸化酪氨酸的相互作用而实现。SOCS3抑制 Jak是通过SH2域而实现(12,13)。除了能够抑制Jak/Stat信号通路，SOCS1和SOCS3基因的SOCS box 能够引起Jak/Stat通路内外蛋白的泛素化诱导蛋白降解(14,15)。SOCS2也能够通过细胞因子诱导，SOCS2的活性主要的是通过SH2域连接到酪氨酸磷酸化受体从而与GH和胰岛素信号通路相连(11,16)。PIAS (激活的Stats的蛋白抑制剂)蛋白, 包括PIAS1, PIAS3, PIASx 和 PIASy (PIAS4), 最初鉴定是基于他们与Stat家族转录因子的相互作用的基础上(16,17)。PIAS1, PIAS3 和 PIASx 分别与Stat1, Stat3 和 Stat4相互作用并抑制它们(17-19)。 PIAS家族包含一个保守的RING 域，它所发挥的作用是SUMO (小的泛素化相关改性剂)连接酶, 偶联SUMO结合酶Ubc9与其底物蛋白导致了对转录因子通过不同的机制而调控，包括NF-κB, c-Jun, Oct-4, p53 和 SMADs。PIAS4 是一个特殊的SUMO-E3 连接酶，能够连接 Ets-1而抑制 Ets-1 依赖的转录，除此之外，也能改变其在细胞核的定位并降低C/EBPδ的转录活性从而增强细胞的增殖和迁移(20,21)。

原厂资料：

Specificity / Sensitivity

Each antibody in this kit recognizes only the specific target protein and does not cross-react with other family members.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Thr585 of human PIAS3 protein, residues surrounding Ala156 of human SOCS1 protein, residues at the carboxy terminus of human SOCS2 protein, or residues surrounding Leu210 of human SOCS3 protein. Polyclonal antibodies are purified by protein A and peptide affinity chromatography. Monoclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser550 of human PIAS1 protein or Lys59 of human PIAS4 protein.

Description

The Jak/Stat Pathway Inhibitors Antibody Sampler Kit provides an economical means to examine several inhibitors of Jak/Stat signaling, including PIAS1, PIAS3, PIAS4, SOCS1, SOCS2, and SOCS3. The kit contains enough primary antibody to perform four western blot experiments with each primary antibody.

Background

Jak (Janus Kinase) and Stat (signal transducer and activator of transcription) proteins are utilized by receptors for a wide varity of ligands including cytokines, hormones, growth factors, and neurotransmitters (1). Jaks and Stats play important roles in oncogenesis, tumor progression, angiogenesis, cell motility, immune responses, and stem cell differentiation (2-5). Therefore, regulation of Jak/Stat signaling is crucial to prevent aberrant signaling which can lead to disease progression. Two methods for regulating Jak/Stat signaling involve SOCS and PIAS proteins (6,7). 
 The SOCS (suppressor or cytokine signaling) family members are negative regulators of cytokine signal transduction that inhibit the Jak/Stat pathway and consist of 8 known members, including the originally identified protein CIS1 (cytokine-inducible SH2-containing protein) and SOCS1-SOCS7. Each SOCS family member contains a central SH2 domain and a conserved carboxy-terminal motif designated as the SOCS box. These proteins are important regulators of cytokine signaling, proliferation, differentiation, and immune responses (8-10). SOCS proteins are involved in regulating over 30 cytokines, including interleukins, growth hormone (GH), interferons, leptin, and leukemia inhibitory factor (7). SOCS1, also known as JAB (Janus Kinase binding protein) and SSI-1 (Stat-induced Stat inhibitor-1), shares the most homology with SOCS3 and both are highly induced by cytokines (7,11). Both SOCS1 and SOCS3 directly inhibit Jak activity; SOCS1 inhibits Jak through an interaction involving a phospohotyrosine located in the kinase activation loop; SOCS3 inhibits Jak via its SH2 domain (12,13). In addition to inhibiting Jak/Stat signaling, the SOCS box of SOCS1 and SOCS3 can trigger ubiquitin-mediated degradation of proteins within and outside the Jak/Stat pathway (14,15). SOCS2 is also incduced upon cytokine stimulation and the activity of SOCS2 has been predominately linked to GH and insulin-like growth factor signaling by binding to tyrosine-phosphorylated receptors via its SH2 domain (11,16). 
 The PIAS (protein inhibitor of activated Stats) proteins, which include PIAS1, PIAS3, PIASx, and PIASy (PIAS4), were originally characterized based on their interaction with the Stat family of transcription factors (16,17). PIAS1, PIAS3, and PIASx interact with and repress Stat1, Stat3, and Stat4, respectively (17-19). The PIAS family contains a conserved RING domain that has been linked to function as a SUMO (small ubiquitin-related modifer) ligase, coupling the SUMO conjugating enzyme Ubc9 with its substrate proteins leading to regulation of transcription factors through distinct mechanisms including NF-κB, c-Jun, Oct-4, p53, and SMADs. PIAS4 is a specific SUMO-E3 ligase for Ets-1 and represses Ets-1 dependent transcription in addition to altering the nuclear localization and reducing the transcriptional activity of C/EBPδ, thereby enhancing cell proliferation and migration (20,21).

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 antibodies.