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Gene Review

Rac1  -  ras-related C3 botulinum toxin substrate 1

Rattus norvegicus

Synonyms: Ras-related C3 botulinum toxin substrate 1, p21-Rac1
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Disease relevance of Rac1

  • Cell lysates from Sf9 insect cells infected with recombinant baculovirus encoding myr 5 exhibited increased GAP activity for RhoA but not for Cdc42Hs or Rac1 [1].
  • CONCLUSIONS: These results suggest that proper Rac1 and AT1R trafficking into caveolae/lipid rafts requires the integrity of microtubules and provide insight into the essential role of microtubules for the spatial-temporal organization of ROS-dependent and caveolae/lipid rafts-dependent AT(1)R signaling linked to vascular hypertrophy [2].
  • Here, we show the crucial role of the ubiquitous Rac1-specific guanine nucleotide exchange factor, Tiam1 (T lymphoma invasion and metastasis 1), in transducing a neurotrophin-mediated change in cell shape [3].
  • Infection of isolated neonatal cardiac myocytes with an adenovirus expressing a constitutively active form of Rac1 (RacV12) enhanced the expression of a kappaB-dependent reporter gene construct and induced the degradation of IkappaBalpha [4].
  • We revealed that IFN-gamma rapidly stimulated activation of Rac1 in C6 astroglioma cells by investigating GST-PAK-PBD-binding ability [5].

High impact information on Rac1

  • These results provide evidence that PDZ proteins target Kalirin-7 to the PSD, where it regulates dendritic morphogenesis through Rac1 signaling to the actin cytoskeleton [6].
  • Kalirin-7, a GDP/GTP exchange factor for Rac1, interacts with PDZ proteins such as PSD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons [6].
  • We have analyzed the function of the Rho proteins Rac1 and CDC42 in the high affinity receptor for IgE (FcepsilonRI)-mediated phagocytosis using transfected rat basophil leukemia (RBL-2H3) mast cells expressing dominant inhibitory forms of CDC42 and Rac1 [7].
  • Fc receptor-mediated phagocytosis requires CDC42 and Rac1 [7].
  • Altogether, our data show that Rac1 and CDC42 are required to coordinate actin filament organization and membrane extension to form phagocytic cups and to allow particle internalization during FcR-mediated phagocytosis [7].

Chemical compound and disease context of Rac1


Biological context of Rac1


Anatomical context of Rac1

  • These results suggest that the phosphorylation of moesin at Thr-558 in PC12 cells by KCl treatment is PKA- and Rac1-dependent and that KCl-induced chloride conductance is involved in the activation of this signaling system [12].
  • Stretching myocytes for 4 min activated RhoA and Rac1 [17].
  • Treatment with 5 mm MbetaCD for 1 h dissociated both RhoA and Rac1 from caveolae [17].
  • We suggest that activation of RhoA or Rac1, localized in a caveolar compartment, is essential for sensing externally applied force and transducing this signal to the actin cytoskeleton and ERK translocation [17].
  • In vascular smooth muscle cells (VSMC) AngII stimulated Rac1 binding to GST-PAK-PBD fusion protein [18].

Associations of Rac1 with chemical compounds

  • Angiotensin II-induced stimulation of p21-activated kinase and c-Jun NH2-terminal kinase is mediated by Rac1 and Nck [18].
  • To determine whether compartmentation of RhoA and Rac1 within caveolae was necessary for stretch signaling, we disrupted caveolae with methyl beta-cyclodextrin (MbetaCD) [17].
  • It was also shown that SMV, by inhibiting Rac1 activity, reversed Ang II-induced increase in intracellular H2O2 production, Akt activation, and p27 protein expression [16].
  • GTP-loading of Rac1 was maintained in CGNs by integrin-mediated (RGD-dependent) cell attachment and trophic support [19].
  • These suggest that tyrosine kinase(s) and phosphatidylinositol 3-kinase (PI 3-kinase) are possibly acting upstream of Rac1 in the LPS signaling to MAPKs [20].
  • We identify betaPix as the guanine nucleotide-exchange factor integrating Rac1 activation to PLD1 and the exocytotic process [21].

Physical interactions of Rac1

  • These results suggest that the ROS, perhaps H(2)O(2), acts as an intracellular signal mediator for NGF-induced neuronal differentiation and that NGF-stimulated ROS production is regulated by Rac1 and a flavoprotein-binding protein similar to the phagocytic NADPH oxidase [22].

Co-localisations of Rac1

  • We demonstrate further that Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts [23].

Regulatory relationships of Rac1


Other interactions of Rac1


Analytical, diagnostic and therapeutic context of Rac1

  • Using a high-throughput immunoblotting screen (BD Powerblot), we found that ToxB markedly reduced the expression of Rac1 and c-Raf, upstream components of a Rac-dependent mitogen-activated protein (MAP) kinase pathway [24].
  • Signal regulatory protein alpha ligation induces macrophage nitric oxide production through JAK/STAT- and phosphatidylinositol 3-kinase/Rac1/NAPDH oxidase/H2O2-dependent pathways [29].
  • In addition, Ha-Ras(V12)-induced DNA synthesis was significantly attenuated by microinjection of recombinant Rac(N17), a dominant negative mutant of Rac1 [30].
  • The cytoskeletal protein actin, a component of focal adhesion plaque protein, vinculin, and the small GTP-binding proteins RhoA and Rac1 were detected by immunohistochemistry in the cells located at the margin of and remote from the wound [31].
  • Mutation analysis and electrophoretic mobility shift assays indicated that the M-CAT element can serve as a binding site for nuclear factors, and this element is important for the induction of CARP promoter activity by p38 and Rac1 [32].


  1. The rat myosin myr 5 is a GTPase-activating protein for Rho in vivo: essential role of arginine 1695. Müller, R.T., Honnert, U., Reinhard, J., Bähler, M. Mol. Biol. Cell (1997) [Pubmed]
  2. Microtubules regulate angiotensin II type 1 receptor and Rac1 localization in caveolae/lipid rafts: role in redox signaling. Zuo, L., Ushio-Fukai, M., Hilenski, L.L., Alexander, R.W. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  3. TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology. Miyamoto, Y., Yamauchi, J., Tanoue, A., Wu, C., Mobley, W.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. The small GTP-binding protein Rac1 induces cardiac myocyte hypertrophy through the activation of apoptosis signal-regulating kinase 1 and nuclear factor-kappa B. Higuchi, Y., Otsu, K., Nishida, K., Hirotani, S., Nakayama, H., Yamaguchi, O., Hikoso, S., Kashiwase, K., Takeda, T., Watanabe, T., Mano, T., Matsumura, Y., Ueno, H., Hori, M. J. Biol. Chem. (2003) [Pubmed]
  5. Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-gamma-stimulated rat astrocytes. Park, E.J., Ji, K.A., Jeon, S.B., Choi, W.H., Han, I.O., You, H.J., Kim, J.H., Jou, I., Joe, E.H. J. Immunol. (2004) [Pubmed]
  6. The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Penzes, P., Johnson, R.C., Sattler, R., Zhang, X., Huganir, R.L., Kambampati, V., Mains, R.E., Eipper, B.A. Neuron (2001) [Pubmed]
  7. Fc receptor-mediated phagocytosis requires CDC42 and Rac1. Massol, P., Montcourrier, P., Guillemot, J.C., Chavrier, P. EMBO J. (1998) [Pubmed]
  8. Statins inhibit beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes via a Rac1-dependent mechanism. Ito, M., Adachi, T., Pimentel, D.R., Ido, Y., Colucci, W.S. Circulation (2004) [Pubmed]
  9. The Ras/Rac1/Cdc42/SEK/JNK/c-Jun cascade is a key pathway by which agonists stimulate DNA synthesis in primary cultures of rat hepatocytes. Auer, K.L., Contessa, J., Brenz-Verca, S., Pirola, L., Rusconi, S., Cooper, G., Abo, A., Wymann, M.P., Davis, R.J., Birrer, M., Dent, P. Mol. Biol. Cell (1998) [Pubmed]
  10. Evidence for the involvement of Tiam1 in axon formation. Kunda, P., Paglini, G., Quiroga, S., Kosik, K., Caceres, A. J. Neurosci. (2001) [Pubmed]
  11. Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Wagner, A.H., Köhler, T., Rückschloss, U., Just, I., Hecker, M. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  12. Chloride conductance is required for the protein kinase A and Rac1-dependent phosphorylation of moesin at Thr-558 by KCl in PC12 cells. Jeon, S., Kim, S., Kim, E., Lee, J.E., Kim, S.J., Juhnn, Y.S., Kim, Y.S., Bae, C.D., Park, J. J. Biol. Chem. (2005) [Pubmed]
  13. Leukotriene B(4) stimulates Rac-ERK cascade to generate reactive oxygen species that mediates chemotaxis. Woo, C.H., You, H.J., Cho, S.H., Eom, Y.W., Chun, J.S., Yoo, Y.J., Kim, J.H. J. Biol. Chem. (2002) [Pubmed]
  14. Cell type-specific regulation of RhoA activity during cytokinesis. Yoshizaki, H., Ohba, Y., Parrini, M.C., Dulyaninova, N.G., Bresnick, A.R., Mochizuki, N., Matsuda, M. J. Biol. Chem. (2004) [Pubmed]
  15. Fibroblast growth factors regulate prolactin transcription via an atypical Rac-dependent signaling pathway. Jackson, T.A., Koterwas, D.M., Morgan, M.A., Bradford, A.P. Mol. Endocrinol. (2003) [Pubmed]
  16. Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27. Zeng, L., Xu, H., Chew, T.L., Chisholm, R., Sadeghi, M.M., Kanwar, Y.S., Danesh, F.R. J. Am. Soc. Nephrol. (2004) [Pubmed]
  17. Initiation and transduction of stretch-induced RhoA and Rac1 activation through caveolae: cytoskeletal regulation of ERK translocation. Kawamura, S., Miyamoto, S., Brown, J.H. J. Biol. Chem. (2003) [Pubmed]
  18. Angiotensin II-induced stimulation of p21-activated kinase and c-Jun NH2-terminal kinase is mediated by Rac1 and Nck. Schmitz, U., Thömmes, K., Beier, I., Wagner, W., Sachinidis, A., Düsing, R., Vetter, H. J. Biol. Chem. (2001) [Pubmed]
  19. Inhibition of Rac GTPase triggers a c-Jun- and Bim-dependent mitochondrial apoptotic cascade in cerebellar granule neurons. Le, S.S., Loucks, F.A., Udo, H., Richardson-Burns, S., Phelps, R.A., Bouchard, R.J., Barth, H., Aktories, K., Tyler, K.L., Kandel, E.R., Heidenreich, K.A., Linseman, D.A. J. Neurochem. (2005) [Pubmed]
  20. Rac GTPase activity is essential for lipopolysaccharide signaling to extracellular signal-regulated kinase and p38 MAP kinase activation in rat-2 fibroblasts. Woo, C.H., Kim, J.H. Mol. Cells (2002) [Pubmed]
  21. betaPIX-activated Rac1 stimulates the activation of phospholipase D, which is associated with exocytosis in neuroendocrine cells. Momboisse, F., Lonchamp, E., Calco, V., Ceridono, M., Vitale, N., Bader, M.F., Gasman, S. J. Cell. Sci. (2009) [Pubmed]
  22. Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species. Suzukawa, K., Miura, K., Mitsushita, J., Resau, J., Hirose, K., Crystal, R., Kamata, T. J. Biol. Chem. (2000) [Pubmed]
  23. Possible role of direct Rac1-Rab7 interaction in ruffled border formation of osteoclasts. Sun, Y., Büki, K.G., Ettala, O., Vääräniemi, J.P., Väänänen, H.K. J. Biol. Chem. (2005) [Pubmed]
  24. Rho family GTPase inhibition reveals opposing effects of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and Janus kinase/signal transducer and activator of transcription signaling cascades on neuronal survival. Loucks, F.A., Le, S.S., Zimmermann, A.K., Ryan, K.R., Barth, H., Aktories, K., Linseman, D.A. J. Neurochem. (2006) [Pubmed]
  25. Intracellular localization and functional effects of P21-activated kinase-1 (Pak1) in cardiac myocytes. Ke, Y., Wang, L., Pyle, W.G., de Tombe, P.P., Solaro, R.J. Circ. Res. (2004) [Pubmed]
  26. PACAP activates Rac1 and synergizes with NGF to activate ERK1/2, thereby inducing neurite outgrowth in PC12 cells. Sakai, Y., Hashimoto, H., Shintani, N., Katoh, H., Negishi, M., Kawaguchi, C., Kasai, A., Baba, A. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  27. Nebivolol Inhibits Superoxide Formation by NADPH Oxidase and Endothelial Dysfunction in Angiotensin II-Treated Rats. Oelze, M., Daiber, A., Brandes, R.P., Hortmann, M., Wenzel, P., Hink, U., Schulz, E., Mollnau, H., von Sandersleben, A., Kleschyov, A.L., Mülsch, A., Li, H., Förstermann, U., Münzel, T. Hypertension (2006) [Pubmed]
  28. Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase. Murasawa, S., Matsubara, H., Mori, Y., Masaki, H., Tsutsumi, Y., Shibasaki, Y., Kitabayashi, I., Tanaka, Y., Fujiyama, S., Koyama, Y., Fujiyama, A., Iba, S., Iwasaka, T. J. Biol. Chem. (2000) [Pubmed]
  29. Signal regulatory protein alpha ligation induces macrophage nitric oxide production through JAK/STAT- and phosphatidylinositol 3-kinase/Rac1/NAPDH oxidase/H2O2-dependent pathways. Alblas, J., Honing, H., de Lavalette, C.R., Brown, M.H., Dijkstra, C.D., van den Berg, T.K. Mol. Cell. Biol. (2005) [Pubmed]
  30. Role of the cytosolic phospholipase A2-linked cascade in signaling by an oncogenic, constitutively active Ha-Ras isoform. Yoo, M.H., Woo, C.H., You, H.J., Cho, S.H., Kim, B.C., Choi, J.E., Chun, J.S., Jhun, B.H., Kim, T.S., Kim, J.H. J. Biol. Chem. (2001) [Pubmed]
  31. Effect of mechanical strain on gastric cellular migration and proliferation during mucosal healing: role of Rho dependent and Rac dependent cytoskeletal reorganisation. Osada, T., Watanabe, S., Tanaka, H., Hirose, M., Miyazaki, A., Sato, N. Gut (1999) [Pubmed]
  32. Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of M-CAT element within the promoter. Aihara, Y., Kurabayashi, M., Saito, Y., Ohyama, Y., Tanaka, T., Takeda, S., Tomaru, K., Sekiguchi, K., Arai, M., Nakamura, T., Nagai, R. Hypertension (2000) [Pubmed]
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