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...
- 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.PubMedPubMedCentralCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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.PubMedPubMedCentralGoogle Scholar