Product Pathways - Cytoskeletal Signaling
PREX1 (D8O8D) Rabbit mAb #13168
|13168S||100 µl (10 western blots)||---||In Stock||---|
|13168||carrier free and custom formulation / quantity||email request|
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|W||1:1000||Human, Monkey||Endogenous||190, 110||Rabbit IgG|
Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting, IF-IC=Immunofluorescence (Immunocytochemistry)
* Product-specific protocol.
Specificity / Sensitivity
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
Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding His770 of human PREX1 protein.
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).
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).
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).
- Welch, H.C. et al. (2002) Cell 108, 809-21.
- Hill, K. et al. (2005) J Biol Chem 280, 4166-73.
- Mayeenuddin, L.H. and Garrison, J.C. (2006) J Biol Chem 281, 1921-8.
- Barber, M.A. et al. (2007) J Biol Chem 282, 29967-76.
- Welch, H.C. et al. (2005) Curr Biol 15, 1867-73.
- Dong, X. et al. (2005) Curr Biol 15, 1874-9.
- Zhao, T. et al. (2007) J Leukoc Biol 81, 1127-36.
- Nie, B. et al. (2010) Cell Signal 22, 770-82.
- Qin, J. et al. (2009) Oncogene 28, 1853-63.
- Wong, C.Y. et al. (2011) J Biol Chem 286, 25813-22.
- Lindsay, C.R. et al. (2011) Nat Commun 2, 555.
- Qian, F. et al. (2012) Arterioscler Thromb Vasc Biol 32, 768-77.
- Naikawadi, R.P. et al. (2012) Circ Res 111, 1517-27.
- Campbell, A.D. et al. (2013) PLoS One 8, e53982.
- Montero, J.C. et al. (2011) Oncogene 30, 1059-71.
- Sosa, M.S. et al. (2010) Mol Cell 40, 877-92.
- Montero, J.C. et al. (2013) Cell Signal 25, 2281-9.
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For Research Use Only. Not For Use In Diagnostic Procedures.
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