| 货号 | 13168S |
| 反应种属 | Human/Monkey |
| 来源宿主 | Rabbit |
| 应用 | W/IF-IC |
| 使用方法 | WB(1:1000) IF-IC (1:400) |
| 供应商 | CST |
| 背景 | <p>Phosphoinositide-3,4,5-triphosphate (PtdIns(3,4,5)P<sub>3</sub>)-dependent Rac exchanger 1 (PREX1) is a Rac-specific GTP-exchange factor (GEF) regulated by heterotrimeric G-protein β/γ subunits and the lipid second messenger PtdIns(3,4,5)P<sub>3</sub> (1-4). PREX1 contains two DEP (Dishevelled, Egl-10, and Pleckstrin homology) domains that coordinate heterotrimeric G-protein signaling. It also contains a Dbl-homology domain, which exhibits Rac-GEF activity, and PH and PDZ domains for interacting with upstream and downstream signaling components (1). Originally shown to modulate cellular migration of neutrophils by Rac2 activation (5-8), it is clear that PREX1 plays a broader role in modulating cell migration. PREX1 promotes metastasis of prostate cancer and melanoma cells, affects endothelial junction integrity, and is required for platelet generation and function (9-14). Research studies suggest that PREX1 plays an essential role in mediating ErbB-dependent signaling events in breast cancer by coordinating Rac activation in response to paracrine signals within the tumor microenvironment. Activation of PREX1 downstream of ErbB3 and EGFR chemokine receptors (CXCR4) promotes Rac activation, increased migration, proliferation, tumorigenesis, and metastasis in breast cancer cells (15,16). Consistent with this observation, deletion of PREX1 expression in mice results in resistance to melanoma metastasis (11). Expression of PREX1 in human tumors transplanted into mice inversely correlates with increased tumor progression and poor survival (15). Additional research studies suggest that PREX Rac-GEF activity is enhanced by phosphorylation in response to growth factors or hormones, and may require coincident dephosphorylation of two PH domain serine residues. The upstream kinases and precise regulatory mechanism remains elusive (15,17).</p>磷脂酰肌醇-3,4,5 - 三磷酸(PtdIns(3,4,5)P<sub>3</sub>)-依赖的Rac交换子1(PREX1)是一个Rac特异性GTP交换因子（GEF）可以被异源三聚体G蛋白β/γ亚基和脂质第二信使PtdIns(3,4,5)P<sub>3</sub>调控 (1-4)。PREX1有两个DEP结构域(Dishevelled, Egl-10,和Pleckstrin homology)和协助异源三聚体G蛋白信号通路。它孩子含有一个Dbl同源结构域，表现了Rac-GEF活性，PH和PDZ结构域可以和上有以及下游的信号分子结合（1）。最初认为Rac2活化会调控中性粒细胞的迁移（5-8），人们已经清楚的认识到PREX1在调控细胞迁移过程中发挥了广泛的作用。PREX1促进了前列腺癌和黑色素瘤细胞的转移，影响内皮细胞交界处的完整性，并且它对于血小板的生成和发挥功能也是必须的(9-14)。研究表明PREX1在介导乳腺癌中ErbB依赖的信号通路时间中，通过协助Rac应激肿瘤微环境中的旁分泌信号而发挥作用。ErbB3 和 EGFR趋化因子受体(CXCR4)下游的PREX1活化能激活Rac，增加乳腺癌细胞的迁移，增殖，肿瘤生成和转移(15,16)。与这一结果相一致，在小鼠中敲除PREX1的表达能使其耐受黑色素瘤转移（11）。人肿瘤组织中的PREX1移植到小鼠中会导致肿瘤的发生以及更低的生存率（15）。更多研究表明省政因子或激素引起的磷酸化能够增强PREX Rac-GEF的活性，这个过程可能还需要同时去磷酸化两个PH结构域的丝氨酸残基。上游信号通路和准确的调控机制尚不明确(15,17)。 |
| 存放说明 | -20C |
| 计算分子量 | 190, 110 |
Confocal immunofluorescent analysis of MCF7 cells, treated with heregulin (10 ng/ml, 5 min; left) or heregulin (10 ng/ml, 5 min) and Wortmannin #9951 (1 μM, 1 hr; center), and MDA-MB-231 cells treated with heregulin (10 ng/ml, 5 min; right), using PREX1 (D8O8D) Rabbit mAb (green). Blue pseudocolor = DRAQ5® #4084 (fluorescent DNA dye).经过heregulin (10 ng/ml, 5 min; 左) 或 heregulin (10 ng/ml, 5 min)和Wortmannin #9951 (1 μM, 1 hr; 中)处理的MCF7细胞，以及使用heregulin (10 ng/ml, 5 min; 右)处理的MDA-MB-231细胞，使用PREX1 (D8O8D) Rabbit mAb（绿色）进行激光共聚焦免疫荧光分析。蓝色假色= DRAQ5® #4084 (fluorescent DNA dye)。 | |
Western blot analysis of extracts from various cell lines using PREX1 (D8O8D) Rabbit mAb (upper) or GAPDH (D16H11) XP® Rabbit mAb #5174 (lower). Differential expression of PREX1 in breast cancer cells is consistent with that described by Sosa, M.S. et al. (2010).使用PREX1 (D8O8D) Rabbit mAb (上)或GAPDH (D16H11) XP® Rabbit mAb #5174 (下)对多种细胞提取物进行western blot分析。PREX1在乳腺癌细胞中的表达水平和来自Sosa, M.S. et al. (2010)的报道一致。 |
