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Rac GTPase

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Encyclopedia of Signaling Molecules

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Synonyms

Rac1: Ras-related C3 botulinum toxin substrate 1; migration-inducing gene 5 protein (MIG5); RAS-like protein TC25

Rac2: Ras-related C3 botulinum toxin substrate 2

Rac3: Ras-related C3 botulinum toxin substrate 3

RhoG: Ras homology growth-related; ARGH

Historical Background and Taxonomy

Rac GTPases comprise one of the eight subfamilies of the Rho (Ras homology) GTPases family, itself a subgroup of the Ras superfamily of small G proteins (Burridge and Wennerberg 2004). They were first identified as a substrate for the bacterial C3-like transferases that block Rho by ADP-ribosylation (hence their name, Ras-related C3 botulinum toxin substrate 1–3), although the C3-like transferases act on Rac rather inefficiently. More effective are the large clostridial cytotoxins (with prototypes the Clostridium difficile toxin A and B) which glycosylate Rac at Thr35, inhibiting its functions by preventing effector coupling (Aktories et al. 2000). Rac GTPases are preferred targets for bacteria...

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References

  • Aktories K, Schmidt G, Just I. Rho GTPases as targets of bacterial protein toxins. Biol Chem. 2000;381:421–6.

    Article  PubMed  CAS  Google Scholar 

  • Alan JK, Lundquist EA. Mutationally activated Rho GTPases in cancer. Small GTPases. 2013;4(3):159–63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Aslan JE, McCarty OJT. Rho GTPases in platelet function. J Thromb Haemost. 2013;11(1):35–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bishop AL, Hall A. Rho GTPases and their effector proteins. Biochem J. 2000;348(Pt 2):241–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bosco EE, Mulloy JC, Zheng Y. Rac1 GTPase: a “Rac” of all trades. Cell Mol Life Sci. 2009;66:370–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Burridge K, Wennerberg K. Rho and Rac take center stage. Cell. 2004;116(2):167–79.

    Article  PubMed  CAS  Google Scholar 

  • Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, Williams DA. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med. 2005;11:886–91.

    Article  PubMed  CAS  Google Scholar 

  • Carrizzo A, Forte M, Lembo M, Formisano L, Puca AA, Vecchione C. Rac1 as a new therapeutic target in cerebro and cardiovascular diseases. Current Drug Targets. 2014;15(13):1231–46.

    Article  PubMed  CAS  Google Scholar 

  • Cho YJ, Zhang B, Kaartinen V, Haataja L, de Curtis I, Groffen J, Heisterkamp N. Generation of rac3 null mutant mice: role of Rac3 in Bcr/Abl-caused lymphoblastic leukemia. Mol Cell Biol. 2005;25:5777–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature. 2002;420:629–35.

    Article  PubMed  CAS  Google Scholar 

  • George A, Pushkaran S, Konstantinidis DG, Koochaki S, Malik P, Mohandas N, Zheng Y, Joiner CH, Kalfa TA. Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood. 2013;121(11):2099–107.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gu Y, Filippi MD, Cancelas JA, Siefring JE, Williams EP, Jasti AC, Harris CE, Lee AW, Prabhakar R, Atkinson SJ, Kwiatkowski DJ, Williams DA. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science. 2003;302:445–9.

    Article  PubMed  CAS  Google Scholar 

  • Goggs R, Harper MMT, Pope RJ, Savage JS, Williams CM, Mundell SJ, Heesom KJ, Bass M, Mellor H, Poole AW. RhoG protein regulates platelet granule secretion and thrombus formation in mice. J Biol Chem. 2013;288(47):34217–29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509–14.

    Article  PubMed  CAS  Google Scholar 

  • Heasman SJ, Ridley AJ. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol. 2008;9:690–701.

    Article  PubMed  CAS  Google Scholar 

  • Hordijk PL. Regulation of NADPH oxidases: the role of Rac proteins. Circ Res. 2006;98:453–62.

    Article  PubMed  CAS  Google Scholar 

  • Ji P, Jayapal SR, Lodish HF. Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2. Nat Cell Biol. 2008;10:314–21.

    Article  PubMed  CAS  Google Scholar 

  • Kalfa TA, Pushkaran S, Mohandas N, Hartwig JH, Fowler VM, Johnson JF, Joiner CH, Williams DA, Zheng Y. Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton. Blood. 2006;108:3637–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kalfa TA, Pushkaran S, Zhang X, Johnson JF, Pan D, Daria D, Geiger H, Cancelas JA, Williams DA, Zheng Y. Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen. Haematologica. 2010;95:27–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Katoh H, Negishi M. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature. 2003;424(24):461–4.

    Article  PubMed  CAS  Google Scholar 

  • Konstantinidis DG, Pushkaran S, Johnson JF, Cancelas JA, Manganaris S, Harris CE, Williams DA, Zheng Y, Kalfa TA. Signaling and cytoskeletal requirements in erythroblast enucleation. Blood. 2012; 119(25): 6118–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010;115:936–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schumacher S, Franke K. miR-124-regulated RhoG. A conductor of neuronal process complexity. Small GTPases. 2013;4(1):42–6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schwartz M. Rho signalling at a glance. J Cell Sci. 2004;117:5457–8.

    Article  PubMed  CAS  Google Scholar 

  • Thomas EK, Cancelas JA, Chae HD, Cox AD, Keller PJ, Perrotti D, Neviani P, Druker BJ, Setchell KD, Zheng Y, Harris CE, Williams DA. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell. 2007;12:467–78.

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Zheng Y. Cell type-specific functions of Rho GTPases revealed by gene targeting in mice. Trends Cell Biol. 2007;17:58–64.

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Pedersen E, Basse A, Lefever T, Peyrollier K, Kapoor S, Mei Q, Karlsson R, Chrostek-Grashoff A, Brakebusch C. Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo. Oncogene. 2010;29:3362–73.

    Article  PubMed  CAS  Google Scholar 

  • Westwick JK, Lambert QT, Clark GJ, Symons M, Van Aelst L, Pestell RG, Der CJ. Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways. Mol Cell Biol. 1997;17:1324–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Williams DA, Tao W, Yang F, Kim C, Gu Y, Mansfield P, Levine JE, Petryniak B, Derrow CW, Harris C, Jia B, Zheng Y, Ambruso DR, Lowe JB, Atkinson SJ, Dinauer MC, Boxer L. Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood. 2000;96:1646–54.

    PubMed  CAS  Google Scholar 

  • Wittmann T, Waterman-Storer CM. Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3β in migrating epithelial cells. J Cell Biol. 2005;169(6):929–39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7015, Cincinnati, OH, 45229-3039, USA

    Diamantis G. Konstantinidis & Theodosia A. Kalfa

Authors
  1. Diamantis G. Konstantinidis
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  2. Theodosia A. Kalfa
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Corresponding author

Correspondence to Theodosia A. Kalfa .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Konstantinidis, D.G., Kalfa, T.A. (2018). Rac GTPase. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_597

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