Prex1

Summary

Gene Symbol: Prex1
Description: phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1
Alias: G630042G04, P-REX1, Setd6, phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein, SET domain containing 6, ptdIns(3,4,5)-dependent Rac exchanger 1
Species: mouse
Products:     Prex1

Top Publications

  1. Yoshizawa M, Kawauchi T, Sone M, Nishimura Y, Terao M, Chihama K, et al. Involvement of a Rac activator,P-Rex1, in neurotrophin-derived signaling and neuronal migration. J Neurosci. 2005;25:4406-19 pubmed
    ..These findings suggest that P-Rex1, which is expressed in a variety of cell types, is activated by extracellular cues such as neurotrophins and contributes to neuronal migration in the developing nervous system. ..
  2. Welch H, Condliffe A, Milne L, Ferguson G, Hill K, Webb L, et al. P-Rex1 regulates neutrophil function. Curr Biol. 2005;15:1867-73 pubmed
    ..In conclusion, P-Rex1 is an important regulator of neutrophil function by mediating a subset of Rac-dependent neutrophil responses. However, P-Rex1 is not an essential regulator of neutrophil chemotaxis and degranulation. ..
  3. Donald S, Humby T, Fyfe I, Segonds Pichon A, Walker S, Andrews S, et al. P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination. Proc Natl Acad Sci U S A. 2008;105:4483-8 pubmed publisher
    ..We conclude that P-Rex1 and P-Rex2 are important regulators of Purkinje cell morphology and cerebellar function. ..
  4. Herter J, Rossaint J, Block H, Welch H, Zarbock A. Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling. Blood. 2013;121:2301-10 pubmed publisher
    ..We conclude that P-Rex1 serves distinct functions in LFA-1 and Mac-1 activation. ..
  5. Dong X, Mo Z, Bokoch G, Guo C, Li Z, Wu D. P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Curr Biol. 2005;15:1874-9 pubmed
    ..Furthermore, P-Rex1 deficiency caused a chemotactic defect that is primarily attributed to a reduction in the migration rate rather than directionality. ..
  6. Pan D, Barber M, Hornigold K, Baker M, Toth J, Oxley D, et al. Norbin Stimulates the Catalytic Activity and Plasma Membrane Localization of the Guanine-Nucleotide Exchange Factor P-Rex1. J Biol Chem. 2016;291:6359-75 pubmed publisher
    ..In summary, we have identified a novel mechanism of P-Rex1 regulation through the GPCR-adaptor protein Norbin, a direct P-Rex1 interacting protein that promotes the Rac-GEF activity and membrane localization of P-Rex1. ..
  7. Lawson C, Donald S, Anderson K, Patton D, Welch H. P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses. J Immunol. 2011;186:1467-76 pubmed publisher
    ..We conclude that P-Rex1 and Vav1 together are the major fMLFR-dependent Dbl family Rac-GEFs in neutrophils and cooperate in the control of fMLF-stimulated neutrophil responses. ..
  8. Qian F, Le Breton G, Chen J, Deng J, Christman J, Wu D, et al. Role for the guanine nucleotide exchange factor phosphatidylinositol-3,4,5-trisphosphate-dependent rac exchanger 1 in platelet secretion and aggregation. Arterioscler Thromb Vasc Biol. 2012;32:768-77 pubmed publisher
    ..These results demonstrate for the first time the presence of P-Rex1 in platelets as well as its role in platelet secretion and aggregation induced by low-dose agonists for GPCR and by collagen. ..
  9. Li J, Chai A, Wang L, Ma Y, Wu Z, Yu H, et al. Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior. Proc Natl Acad Sci U S A. 2015;112:E6964-72 pubmed publisher
    ..Together, our findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs. ..

More Information

Publications22

  1. Balamatsias D, Kong A, Waters J, Sriratana A, Gurung R, Bailey C, et al. Identification of P-Rex1 as a novel Rac1-guanine nucleotide exchange factor (GEF) that promotes actin remodeling and GLUT4 protein trafficking in adipocytes. J Biol Chem. 2011;286:43229-40 pubmed publisher
  2. Boyle K, Gyori D, Sindrilaru A, Scharffetter Kochanek K, Taylor P, Mócsai A, et al. Class IA phosphoinositide 3-kinase β and δ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae. J Immunol. 2011;186:2978-89 pubmed publisher
    ..These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae. ..
  3. Schneider M, Dahlhoff M, Horst D, Hirschi B, Trulzsch K, Müller Höcker J, et al. A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation. PLoS ONE. 2010;5:e14325 pubmed publisher
  4. Wang Z, Dong X, Li Z, Smith J, Wu D. Lack of a significant role of P-Rex1, a major regulator of macrophage Rac1 activation and chemotaxis, in atherogenesis. Prostaglandins Other Lipid Mediat. 2008;87:9-13 pubmed publisher
    ..P-Rex1 is one of the major GEFs in macrophage regulating Rac1 activation and chemotaxis. ..
  5. Lindsay C, Lawn S, Campbell A, Faller W, Rambow F, Mort R, et al. P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nat Commun. 2011;2:555 pubmed publisher
    ..We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans. ..
  6. Ebi H, Costa C, Faber A, Nishtala M, Kotani H, Juric D, et al. PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1. Proc Natl Acad Sci U S A. 2013;110:21124-9 pubmed publisher
    ..In addition, P-Rex1 may serve as a biomarker to predict response to single-agent PI3K inhibitors within this subset of breast cancers. ..
  7. Jackson C, Welch H, Bellamy T. Control of cerebellar long-term potentiation by P-Rex-family guanine-nucleotide exchange factors and phosphoinositide 3-kinase. PLoS ONE. 2010;5:e11962 pubmed publisher
    ..Our data suggest that a PI3K/P-Rex/Rac pathway is required for late phase LTP in the mouse cerebellum, and that other PI3K targets, which remain to be discovered, control LTP induction. ..
  8. Marei H, Carpy A, Woroniuk A, Vennin C, White G, Timpson P, et al. Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration. Nat Commun. 2016;7:10664 pubmed publisher
    ..In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner. ..
  9. Naikawadi R, Cheng N, Vogel S, Qian F, Wu D, Malik A, et al. A critical role for phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 in endothelial junction disruption and vascular hyperpermeability. Circ Res. 2012;111:1517-27 pubmed publisher
    ..Our data identify P-Rex1 as a critical mediator of vascular barrier disruption. Targeting P-Rex1 may effectively protect against TNF-?- and lipopolysaccharide-induced endothelial junction disruption and vascular hyperpermeability. ..
  10. Damoulakis G, Gambardella L, Rossman K, Lawson C, Anderson K, Fukui Y, et al. P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. J Cell Sci. 2014;127:2589-600 pubmed publisher
    ..These findings thus have broad implications for our understanding of GPCR signalling to Rho GTPases and the actin cytoskeleton. ..
  11. Lindsay C, Li A, Faller W, Ozanne B, Welch H, Machesky L, et al. A Rac1-independent role for P-Rex1 in melanoblasts. J Invest Dermatol. 2015;135:314-318 pubmed publisher
  12. Pan D, Amison R, Riffo Vasquez Y, Spina D, Cleary S, Wakelam M, et al. P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation. Blood. 2015;125:1146-58 pubmed publisher
    ..Therefore, platelet P-Rex and Vav family Rac-GEFs play important proinflammatory roles in leukocyte recruitment. ..
  13. Liang Q, Cheng N, Zhang G, Liang Y, Qian F, Wu D, et al. Identification of P-Rex1 as an anti-inflammatory and anti-fibrogenic target for pulmonary fibrosis. Sci Rep. 2016;6:25785 pubmed publisher
    ..These findings identify P-Rex1 as a novel player of PF, suggesting that targeting P-Rex1 may simultaneously block the inflammatory and fibrogenic processes of PF. ..