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Rac1 is a GTPase that is involved in the regulation of the cell cycle, cell-cell adhesion, motility, and differentiation.1 Rac1 is activated by its interaction with specific guanine nucleotide exchange factors (GEFs). NSC23766 is a cell-permeable, reversible inhibitor of Rac1 activation by the Rac-specific GEFs TrioN and Tiam 1 (IC50 = 50 μM).2 It has no effect on the closely related GTPases, Cdc42, and RhoA. NSC 23766 has been used to investigate the role of Rac1 in such diverse cellular functions as stem cell mobilization, epithelial cell migration, angiogenesis, leukemia cell migration and growth, and gene expression.3,4,5,6,7
1
Bosco, E.E., Mulloy, J.C., and Zheng, Y. Rac1 GTPase: A “Rac” of all trades. Cell Mol Life Sci66370-374(2009).
2
Gao, Y., Dickerson, J.B., Guo, F., et al. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA101(20)7618-7623(2004).
4
Rao, J.N., Liu, S.V., Zou, T., et al. Rac1 promotes intestinal epithelial restitution by increasing Ca2+ influx through interaction with phospholipase C-γ1 after wounding. Am J Physiol Cell Physiol295C1499-C1509(2008).
5
Sawada, N., Salomone, S., Kim, H., et al. Regulation of endothelial nitric oxide synthase and postnatal angiogenesis by Rac1. Circ Res103360-368(2008).
6
Wang, J., Rao, Q., Wang, M., et al. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth. Biochem Biophys Res Commun386769-774(2009).
7
Vallon, M., Rohde, F., Janssen, K., et al. Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation. Exp Cell Res316412-421(2010).
Bosco, E.E., Mulloy, J.C., and Zheng, Y. Rac1 GTPase: A “Rac” of all trades. Cell Mol Life Sci66370-374(2009).
Cancelas, J.A., Lee, A.W., Prabhakar, R., et al. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med11(8)886-891(2005).
Rao, J.N., Liu, S.V., Zou, T., et al. Rac1 promotes intestinal epithelial restitution by increasing Ca2+ influx through interaction with phospholipase C-γ1 after wounding. Am J Physiol Cell Physiol295C1499-C1509(2008).
Wang, J., Rao, Q., Wang, M., et al. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth. Biochem Biophys Res Commun386769-774(2009).
Vallon, M., Rohde, F., Janssen, K., et al. Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation. Exp Cell Res316412-421(2010).
Gao, Y., Dickerson, J.B., Guo, F., et al. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA101(20)7618-7623(2004).
Sawada, N., Salomone, S., Kim, H., et al. Regulation of endothelial nitric oxide synthase and postnatal angiogenesis by Rac1. Circ Res103360-368(2008).