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Gene Review

RAC1  -  ras-related C3 botulinum toxin substrate 1...

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Disease relevance of RAC1

  • The neutrophil NADPH oxidase activation factors, p47, p67 and the small guanosine-nucleotide-binding regulatory (G) protein Rac1, were expressed in a baculovirus/insect cell system and purified [1].

High impact information on RAC1


Biological context of RAC1


Anatomical context of RAC1

  • In bovine adrenal chromaffin cells, we found Rac1, but not Cdc42, to be rapidly and selectively activated by secretory stimuli using an assay selective for the activated GTPases [8].
  • These findings suggest that Rac1, in part, functions to modulate secretion through actions on the cytoskeleton [8].
  • Taken together, these data suggest a model by which two distinct signaling pathways, the ERK and Rac1 pathways, positively regulate cyclin D(1) and smooth muscle growth [4].
  • We showed that it mediates cytoskeletal reorganizations in bovine aortic endothelial (BAE) and Chinese hamster ovary (CHO) cells and does so by acting upstream of Rac1 activation [9].
  • Role of rac1 in fibronectin-induced adhesion and motility of human corneal epithelial cells [5].

Associations of RAC1 with chemical compounds

  • Likewise, overexpression of vRAC, a constitutively active RAC1, increased caspase-3 activity to the same extent as palmitate alone [10].
  • Overexpression of an N-terminal fragment of p67(phox), a component of NADPH oxidase which interacts with Rac1, attenuated PDGF-induced cyclin D(1) promoter activity, whereas overexpression of the wild-type p67 did not [4].
  • Pretreatment with ebselen, catalase, and the flavoprotein inhibitor diphenylene iodonium each attenuated PDGF- and Rac1-mediated cyclin D(1) promoter activation, while having no effect on the induction of cyclin D(1) by mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase-1 (MEK1), the upstream activator of ERKs [4].
  • Rac1 forms part of the NADPH oxidase complex that generates reactive oxygen species such as H(2)O(2) [4].
  • By confocal immunofluorescence analysis, we found that Rac1 and Cdc42 are exclusively localized in the subplasmalemmal region in both resting and nicotine-stimulated cells [11].

Regulatory relationships of RAC1

  • We exploited the p21-activated kinase pulldown assay to identify proteins associated with activated Rac1 and found that epinephrine stimulated the association of eNOS with Rac1; epinephrine-stimulated eNOS-Rac1 interactions were blocked by the beta(3)AR antagonist SR59230A [12].


  1. Activation of the O2(-)-generating NADPH oxidase in a semi-recombinant cell-free system. Assessment of the function of Rac in the activation process. Fuchs, A., Dagher, M.C., Jouan, A., Vignais, P.V. Eur. J. Biochem. (1994) [Pubmed]
  2. Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Honda, A., Nogami, M., Yokozeki, T., Yamazaki, M., Nakamura, H., Watanabe, H., Kawamoto, K., Nakayama, K., Morris, A.J., Frohman, M.A., Kanaho, Y. Cell (1999) [Pubmed]
  3. Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression. Tzima, E., Del Pozo, M.A., Kiosses, W.B., Mohamed, S.A., Li, S., Chien, S., Schwartz, M.A. EMBO J. (2002) [Pubmed]
  4. Characterization of a Rac1 signaling pathway to cyclin D(1) expression in airway smooth muscle cells. Page, K., Li, J., Hodge, J.A., Liu, P.T., Vanden Hoek, T.L., Becker, L.B., Pestell, R.G., Rosner, M.R., Hershenson, M.B. J. Biol. Chem. (1999) [Pubmed]
  5. Role of rac1 in fibronectin-induced adhesion and motility of human corneal epithelial cells. Kimura, K., Kawamoto, K., Teranishi, S., Nishida, T. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  6. Cdc42, but not RhoA, regulates cyclin D1 expression in bovine tracheal myocytes. Bauerfeld, C.P., Hershenson, M.B., Page, K. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  7. Roles of microtubule dynamics and small GTPase Rac in endothelial cell migration and lamellipodium formation under flow. Hu, Y.L., Li, S., Miao, H., Tsou, T.C., del Pozo, M.A., Chien, S. J. Vasc. Res. (2002) [Pubmed]
  8. Facilitation of Ca(2+)-dependent exocytosis by Rac1-GTPase in bovine chromaffin cells. Li, Q., Ho, C.S., Marinescu, V., Bhatti, H., Bokoch, G.M., Ernst, S.A., Holz, R.W., Stuenkel, E.L. J. Physiol. (Lond.) (2003) [Pubmed]
  9. Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin-induced actin filament assembly and cell spreading. Kulkarni, S., Goll, D.E., Fox, J.E. J. Biol. Chem. (2002) [Pubmed]
  10. Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Cacicedo, J.M., Benjachareowong, S., Chou, E., Ruderman, N.B., Ido, Y. Diabetes (2005) [Pubmed]
  11. Involvement of Rho GTPases in calcium-regulated exocytosis from adrenal chromaffin cells. Gasman, S., Chasserot-Golaz, S., Popoff, M.R., Aunis, D., Bader, M.F. J. Cell. Sci. (1999) [Pubmed]
  12. Epinephrine regulation of the endothelial nitric-oxide synthase: roles of RAC1 and beta3-adrenergic receptors in endothelial NO signaling. Kou, R., Michel, T. J. Biol. Chem. (2007) [Pubmed]
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