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, 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 since they act as molecular switches in a multitude of signaling processes, regulating many fundamental cellular functions, including actin cytoskeleton, cell adhesion, motility and migration, vesicular transport pathways and cytokinesis, reactive oxygen species (ROS)production via NADPH oxidase, as well as cell...
This is a preview of subscription content, log in via an institution to check access.
References
Aktories K, Schmidt G, Just I. Rho GTPases as targets of bacterial protein toxins. Biol Chem. 2000;381:421–6.
Bishop AL, Hall A. Rho GTPases and their effector proteins. Biochem J. 2000;348(Pt 2):241–55.
Bosco EE, Mulloy JC, Zheng Y. Rac1 GTPase: a “Rac” of all trades. Cell Mol Life Sci. 2009;66:370–4.
Burridge K, Wennerberg K. Rho and Rac take center stage. Cell. 2004;116(2):167–79.
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.
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.
Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature. 2002;420:629–35.
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.
Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509–14.
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.
Hordijk PL. Regulation of NADPH oxidases: the role of Rac proteins. Circ Res. 2006;98:453–62.
Ji P, Jayapal SR, Lodish HF. Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2. Nat Cell Biol. 2008;10:314–21.
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.
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.
Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010;115:936–47.
Schwartz M. Rho signalling at a glance. J Cell Sci. 2004;117:5457–8.
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.
Wang L, Zheng Y. Cell type-specific functions of Rho GTPases revealed by gene targeting in mice. Trends Cell Biol. 2007;17:58–64.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this entry
Cite this entry
Konstantinidis, D., Kalfa, T.A. (2012). Rac GTPases. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_597
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0461-4_597
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0460-7
Online ISBN: 978-1-4419-0461-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences