PREX1 (D8O8D) Rabbit mAb

• 产品编号：CST-13168S      品牌：CST       原厂货号：13168S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

</p>PREX1 (D8O8D) Rabbit mAb可以识别内源性总的PREX1蛋白。该抗体可以识别人PREX1的亚型1(190 kDa)和亚型2 (110 kDa)，但是并未发现能与人PREX2蛋白结合。</p> 单克隆抗体由合成磷酸肽段免疫动物产生，该肽段与人PREX1蛋白His770附近氨基酸一致。</p>磷脂酰肌醇-3,4,5 - 三磷酸(PtdIns(3,4,5)P₃)-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)P₃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)。

1. Welch, H.C. et al. (2002) Cell 108, 809-21.
2. Hill, K. et al. (2005) J Biol Chem 280, 4166-73.
3. Mayeenuddin, L.H. and Garrison, J.C. (2006) J Biol Chem 281, 1921-8.
4. Barber, M.A. et al. (2007) J Biol Chem 282, 29967-76.
5. Welch, H.C. et al. (2005) Curr Biol 15, 1867-73.
6. Dong, X. et al. (2005) Curr Biol 15, 1874-9.
7. Zhao, T. et al. (2007) J Leukoc Biol 81, 1127-36.
8. Nie, B. et al. (2010) Cell Signal 22, 770-82.
9. Qin, J. et al. (2009) Oncogene 28, 1853-63.
10. Wong, C.Y. et al. (2011) J Biol Chem 286, 25813-22.
11. Lindsay, C.R. et al. (2011) Nat Commun 2, 555.
12. Qian, F. et al. (2012) Arterioscler Thromb Vasc Biol 32, 768-77.
13. Naikawadi, R.P. et al. (2012) Circ Res 111, 1517-27.
14. Campbell, A.D. et al. (2013) PLoS One 8, e53982.
15. Montero, J.C. et al. (2011) Oncogene 30, 1059-71.
16. Sosa, M.S. et al. (2010) Mol Cell 40, 877-92.
17. Montero, J.C. et al. (2013) Cell Signal 25, 2281-9.

原厂资料：

Specificity / Sensitivity

<p>PREX1 (D8O8D) Rabbit mAb recognizes endogenous levels of total PREX1 protein. This antibody will recognize both isoform 1 (190 kDa) and isoform 2 (110 kDa) human PREX1, but has not been observed to cross-react with human PREX2 protein.

Source / Purification

<p>Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding His770 of human PREX1 protein

Background

<p>Phosphoinositide-3,4,5-triphosphate (PtdIns(3,4,5)P₃)-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)P₃ (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).

1. Welch, H.C. et al. (2002) Cell 108, 809-21.
2. Hill, K. et al. (2005) J Biol Chem 280, 4166-73.
3. Mayeenuddin, L.H. and Garrison, J.C. (2006) J Biol Chem 281, 1921-8.
4. Barber, M.A. et al. (2007) J Biol Chem 282, 29967-76.
5. Welch, H.C. et al. (2005) Curr Biol 15, 1867-73.
6. Dong, X. et al. (2005) Curr Biol 15, 1874-9.
7. Zhao, T. et al. (2007) J Leukoc Biol 81, 1127-36.
8. Nie, B. et al. (2010) Cell Signal 22, 770-82.
9. Qin, J. et al. (2009) Oncogene 28, 1853-63.
10. Wong, C.Y. et al. (2011) J Biol Chem 286, 25813-22.
11. Lindsay, C.R. et al. (2011) Nat Commun 2, 555.
12. Qian, F. et al. (2012) Arterioscler Thromb Vasc Biol 32, 768-77.
13. Naikawadi, R.P. et al. (2012) Circ Res 111, 1517-27.
14. Campbell, A.D. et al. (2013) PLoS One 8, e53982.
15. Montero, J.C. et al. (2011) Oncogene 30, 1059-71.
16. Sosa, M.S. et al. (2010) Mol Cell 40, 877-92.
17. Montero, J.C. et al. (2013) Cell Signal 25, 2281-9.

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