GTP-binding proteins of the Rho/Rac family: Regulation, effectors and functions in vivo

BioEssays

Volumn 29, Issue 4, 2007, Pages 356-370

  Bustelo, Xosé R ^a   Sauzeau, Vincent ^a   Berenjeno, Inmaculada M ^a  

^a UNIVERSITY OF SALAMANCA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

GUANINE NUCLEOTIDE BINDING PROTEIN; RAC PROTEIN; RHO FACTOR;

CELL CYCLE; CELL DIFFERENTIATION; CELL POLARITY; GENETIC ANALYSIS; IN VIVO STUDY; NONHUMAN; PROTEIN FUNCTION; REVIEW;

ANIMALS; GENE EXPRESSION REGULATION; PHYLOGENY; PROTEIN BINDING; RAC GTP-BINDING PROTEINS; RHO GTP-BINDING PROTEINS; TRANSCRIPTION, GENETIC;

EID: 34247175312     PISSN: 02659247     EISSN: None     Source Type: Journal    
DOI: 10.1002/bies.20558     Document Type: Review

References (100)

1. Madaule P, Axel R. 1985. A novel ras-related gene family. Cell 41:31-40.
2. Etienne-Manneville S, Hall A. 2002. Rho GTPases in cell biology. Nature 420:629-635.
3. Boettner B, Van Aelst L. 2002. The role of Rho GTPases in disease development. Gene 286:155-174.
4. Sanai E, Marshall CJ. 2002. RHO-GTPases and cancer. Nat Rev Cancer 2:133-142.
5. Jaffe AB, Hall A. 2005. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247-269.
6. Rossman KL, Der CJ, Sondek J. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 6:167-180.
7. Peck J, Douglas Gt, Wu CH, Burbelo PD. 2002. Human RhoGAP domain-containing proteins: structure, function and evolutionary relationships. FEBS Lett 528:27-34.
8. Winter-Vann AM, Casey PJ. 2005. Post-prenylation-processing enzymes as new targets in oncogenesis. Nat Rev Cancer 5:405-412.
9. Casey PJ, Seabra MC. 1996. Protein prenyltransferases. J Biol Chem 271:5289-5292.
10. Choy E, Chiu VK, Silletti J, Feoktistov M, Morimoto T, et al. 1999. Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi. Cell 98:69-80.
11. Boyartchuk VL, Ashby MN, Rine J. 1997. Modulation of Ras and a-factor function by carboxyl-terminal proteolysis. Science 275:1796-1800.
12. Dai Q, Choy E, Chiu V, Romano J, Slivka SR, et al. 1998. Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum. J Biol Chem 273:15030-15034.
13. Michaelson D, Ali W, Chiu VK, Bergo M, Silletti J, et al. 2005. Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases. Mol Biol Cell 16:1606-1616.
14. Lebowitz PF, Davide JP, Prendergast GC. 1995. Evidence that farnesyltransferase inhibitors suppress Ras transformation by interfering with Rho activity. Mol Cell Biol 15:6613-6622.
15. Filippi MD, Harris CE, Meller J, Gu Y, Zheng Y, et al. 2004. Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and Chemotaxis in neutrophils. Nat Immunol 5:744-751.
16. Prieto-Sanchez RM, Bustelo XR. 2003. Structural basis for the signaling specificity of RhoG and Rad GTPases. J Biol Chem 278:37916-37925.
17. ten Klooster JP, Jaffer ZM, Chernoff J, Hordijk PL. 2006. Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix. J Cell Biol 172:759-769.
18. DerMardirossian C, Bokoch GM. 2005. GDIs: central regulatory molecules in Rho GTPase activation. Trends Cell Biol 15:356-363.
19. del Pozo MA, Price LS, Alderson NB, Ren XD, Schwartz MA. 2000. Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. Embo J 19:2008-2014.
20. Del Pozo MA, Kiosses WB, Alderson NB, Meller N, Hahn KM, et al. 2002. Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nat Cell Biol 4:232-239.
21. Yamashita T, Tohyama M. 2003. The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci 6:461-467.
22. Price LS, Langeslag M, ten Klooster JP, Hordijk PL, Jalink K, et al. 2003. Calcium signaling regulates translocation and activation of Rac. J Biol Chem 278:39413-39421.
23. DerMardirossian C, Schnelzer A, Bokoch GM. 2004. Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol Cell 15:117-127.
24. Bishop AL, Hall A. 2000. Rho GTPases and their effector proteins. Biochem J 348Pt 2:241-255.
25. del Pozo MA, Alderson NB, Kiosses WB, Chiang HH, Anderson RG, et al. 2004. Integrins regulate Rac targeting by internalization of membrane domains. Science 303:839-842.
26. Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R. 1989. rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem 264:16378-16382.
27. Bolis A, Corbetta S, Cioce A, de Curtis I. 2003. Differential distribution of Rad and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiation. Eur J Neurosci 18:2417-2424.
28. Zalcman G, Closson V, Linares-Cruz G, Lerebours F, Honore N, et al. 1995. Regulation of Ras-related RhoB protein expression during the cell cycle. Oncogene 10:1935-1945.
29. Vincent S, Jeanteur P, Fort P. 1992. Growth-regulated expression of rhoG, a new member of the ras homolog gene family. Mol Cell Biol 12:3138-3148.
30. Jahner D, Hunter T. 1991. The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. MoI Cell Biol 11:3682-3690.
31. Fritz G, Kaina B. 1997. rhoB encoding a UV-inducible Ras-related small GTP-binding protein is regulated by GTPases of the Rho family and independent of JNK, ERK, and p38 MAP kinase. J Biol Chem 272:30637-30644.
32. Fritz G, Kaina B, Aktories K. 1995. The ras-related small GTP-binding protein RhoB is immediate-early inducible by DNA damaging treatments. J Biol Chem 270:25172-25177.
33. Fritz G, Kaina B. 2001. Transcriptional activation of the small GTPase gene rhoB by genotoxic stress is regulated via a CCAAT element. Nucleic Acids Res 29:792-798.
34. Jiang K, Sun J, Cheng J, Djeu JY, Wei S, et al. 2004, Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Mol Cell Biol 24:5565-5576.
35. Tao W, Pennica D, Xu L, Kalejta RF, Levine AJ. 2001. Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1. Genes Dev 15:1796-1807.
36. Wang HR, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, et al. 2003. Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science 302:1775-1779.
37. Tu S, Cerione RA. 2001. Cdc42 is a substrate for caspases and influences Fas-induced apoptosis. J Biol Chem 276:19656-19663.
38. Shutes A, Berzat AC, Cox AD, Der CJ. 2004. Atypical mechanism of regulation of the Wrch-1 Rho family small GTPase. Curr Biol 14:2052-2056.
39. Forget MA, Desrosiers RR, Gingras D, Beliveau R. 2002. Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes. Biochem J 361:243-254.
40. Lang P, Gesbert F, Delespine-Carmagnat M, Stancou R, Pouchelet M, et al. 1996. Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. Embo J 15:510-519.
41. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y. 2004. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 101:7618-7623.
42. Pelish HE, Peterson JR, Salvarezza SB, Rodriguez-Boulan E, Chen JL, et at. 2006. Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro. Nat Chem Biol 2:39-46.
43. Phee H, Abraham RT, Weiss A. 2005. Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1. Nat Immunol 6:608-617.
44. Brown MC, West KA, Turner CE. 2002. Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal adhesions involves a multistep activation pathway. MoI Biol Cell 13:1550-1565.
45. Dharmawardhane S, Sanders LC, Martin SS, Daniels RH, Bokoch GM. 1997. Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. J Cell Biol 138:1265-1278.
46. Mellor H, Flynn P, Nobes CD, Hall A, Parker PJ. 1998. PRK1 is targeted to endosomes by the small GTPase, RhoB. J Biol Chem 273:4811-4814.
47. Kosako H, Yoshida T, Matsumura F, Ishizaki T, Narumiya S, et al. 2000. Rho-kinase/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin/radixin/moesin proteins at the cleavage furrow. Oncogene 19:6059-6064.
48. Mukai H, Kitagawa M, Shibata H, Takanaga H, Mori K, et al. 1994. Activation of PKN, a novel 120-kDa protein kinase with leucine zipper-like sequences, by unsaturated fatty acids and by limited proteolysis. Biochem Biophys Res Commun 204:348-356.
49. Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW. 2002. Mechanism of regulation of WAVE1-induced actin nucleation by Rad and Nek. Nature 418:790-793.
50. Joberty G, Perlungher RR, Sheffield PJ, Kinoshita M, Noda M, et al. 2001. Borg proteins control septin organization and are negatively regulated by Cdc42. Nat Cell Biol 3:861-866.
51. Callow MG, Zozulya S, Gishizky ML, Jallal B, Smeal T. 2005. PAK4 mediates morphological changes through the regulation of GEF- H1. J Cell Sci 118:1861-1872.
52. Zhao L, Ma QL, Calon F, Harris-White ME, Yang F, et al. 2006. Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease. Nat Neurosci 9:234-242.
53. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, et al. 1997. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389:990-994.
54. Nagumo H, Sasaki Y, Ono Y, Okamoto H, Seto M, et al. 2000. Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells. Am J Physiol Cell Physiol 278:057-C65.
55. Mueller BK, Mack H, Teusch N. 2005. Rho kinase, a promising drug target for neurological disorders. Nat Rev Drug Discov 4:387-398.
56. Bustelo XR. 2002. Understanding Rho/Rac biology in T-cells using animal models. Bioessays 24:602-612.
57. Turner M, Billadeau DD. 2002. VAV proteins as signal integrators for multi-subunit immune-recognition receptors. Nat Rev Immunol 2:476-486.
58. Sugihara K, Nakatsuji N, Nakamura K, Nakao K, Hashimoto R, et al. 1998. Rac1 is required for the formation of three germ layers during gastrulation. Oncogene 17:3427-3433.
59. Corbetta S, Gualdoni S, Albertinazzi C, Paris S, Croci L, et al. 2005. Generation and characterization of Rac3 knockout mice. Mol Cell Biol 25:5763-5776.
60. Vigorito E, Bell S, Hebeis BJ, Reynolds H, McAdam S, et al. 2004. Immunological function in mice lacking the Rac-related GTPase RhoG. Mol Cell Biol 24:719-729.
61. Condliffe AM, Webb LM, Ferguson GJ, Davidson K, Turner M, et al. 2006. RhoG regulates the neutrophil NADPH oxidase. J Immunol 176: 5314-5320.
62. Gu Y, Filippi MD, Cancelas JA, Siefring JE, Williams EP, et al. 2003. Hematopoietic cell regulation by Rad and Rac2 guanosine triphosphatases. Science 302:445-449.
63. Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, et al. 2005. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med 11:886-891.
64. Yu H, Leitenberg D, Li B, Flavell RA. 2001. Deficiency of small GTPase Rac2 affects T cell activation. J Exp Med 194:915-926.
65. Li B, Yu H, Zheng W, Voll R, Na S, et al. 2000. Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation. Science 288: 2219-2222.
66. Croker BA, Tarlinton DM, Cluse LA, Tuxen AJ, Light A, et al. 2002. The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and Chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes. J Immunol 168:3376-3386.
67. Walmsley MJ, Ooi SK, Reynolds LF, Smith SH, Ruf S, et al. 2003. Critical roles for Rad and Rac2 GTPases in B cell development and signaling. Science 302:459-462.
68. Kim C, Dinauer MC. 2001. Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways. J Immunol 166:1223-1232.
69. Li S, Yamauchi A, Marchai CC, Molitoris JK, Quilliam LA, et al. 2002. Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions. J Immunol 169:5043-5051.
70. Glogauer M, Marchal CC, Zhu F, Worku A, Clausen BE, et al. 2003. Rad deletion in mouse neutrophils has selective effects on neutrophil functions. J Immunol 170:5652-5657.
71. Sun CX, Downey GP, Zhu F, Koh AL, Thang H, et al. 2004. Rac1 is the small GTPase responsible for regulating the neutrophil Chemotaxis compass. Blood 104:3758-3765.
72. Pestonjamasp KN, Forster C, Sun C, Gardiner EM, Bohl B, et al. 2006. Rad links leading edge and uropod events through Rho and myosin activation during Chemotaxis. Blood 108:2814-2820
73. Yamauchi A, Kim C, Li S, Marchai CC, Towe J, et al. 2004. Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. J Immunol 173:5971-5979.
74. Wells CM, Walmsley M, Ooi S, Tybulewicz V, Ridley AJ. 2004. Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration. J Cell Sci 117:1259-1268.
75. McCarty OJ, Larson MK, Auger JM, Kalia N, Atkinson BT, et al. 2005. Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow. J Biol Chem 280:39474-39484.
76. Thurnherr T, Benninger Y, Wu X, Chrostek A, Krause SM, et al. 2006. Cdc42 and Rad signaling are both required for and act synergistically in the correcl formation of myelin sheaths in the CNS. J Neurosci 26:10110-10119.
77. Chrostek A, Wu X, Quondamatteo F, Hu R, Sanecka A, et al. 2006. Rac1 is crucial for hair follicle integrity but is not essential for maintenance of the epidermis. Mol Cell Biol 26:6957-6970.
78. Benvenuti F, Hugues S, Walmsley M, Ruf S, Fetler L, et al. 2004. Requirement of Rad and Rac2 expression by mature dendritic cells for T cell priming. Science 305:1150-1153.
79. Qu J, Li X, Ncvitch BG, Zheng Y, Kohn M, et al. 2003. PAK4 kinase is essential for embryonic viability and for proper neuronal development. Mol Cell Biol 23:7122-7133.
80. Yamazaki D, Suetsugu S, Miki H, Kataoka Y, Nishikawa S, et al. 2003. WAVE2 is required for directed cell migration and cardiovascular development. Nature 424:452-456
81. Yan C, Martinez-Quiles N, Eden S, Shibata T, Takeshima F, et al. 2003. WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. Embo J 22:3602-3612.
82. Soderling SH, Langeberg LK, Soderling JA, Davee SM, Simerly R, et al. 2003. Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Proc Natl Acad Sci USA 100:1723-1728.
83. Li X, Minden A. 2003. Targeted disruption of the gene for the PAK5 kinase in mice. Mol Cell Biol 23:7134-7142.
84. Liu AX, Rane N, Liu JP, Prendergast GC. 2001. RhoB is dispensable for mouse development, but it modifies susceptibility to tumor formation as well as cell adhesion and growth factor signaling in transformed cells. MoI Cell Biol 21:6906-6912.
85. Hakem A, Sanchez-Sweatman O, You-Ten A, Duncan G, Wakeham A, et al. 2005. RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes Dev 19:1974-1979.
86. Thumkeo D, Shimizu Y, Sakamoto S, Yamada S, Narumiya S. 2005. ROCK-I and ROCK-II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo. Genes Cells 10:825-834.
87. Shimizu Y, Thumkeo D, Keel J, Ishizaki T, Oshima H, et al. 2005. ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol 168:941-953.
88. Thumkeo D, Keel J, Ishizaki T, Hirose M, Nonomura K, et al. 2003. Targeted disruption of the mouse rho-associated kinase 2 gene results in intrauterine growth retardation and fetal death. Mol Cell Biol 23:5043-5055.
89. Di Cunto F, Imarisio S, Hirsch E, Broccoli V, Bulfone A, et al. 2000. Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis. Neuron 28:115-127.
90. Cunto FD, Imarisio S, Camera P, Boitani C, Altruda F, et al. 2002. Essential role of citron kinase in cytokinesis of spermatogenic precursors. J Cell Sci 115:4819-4826.
91. Takahashi H, Koshimizu U, Miyazaki J, Nakamura T. 2002. Impaired spermatogenic ability of testicular germ cells in mice deficient in the LIM-kinase 2 gene. Dev Biol 241:259-272.
92. Behrends J, Clement S, Pajak B, Pohl V, Maenhaut C, et al. 2005. Normal thyroid structure and function in rhophilin 2-deficient mice. Mol Cell Biol 25:2846-2852.
93. Chen F, Ma L, Parrini MC, Mao X, Lopez M, et al. 2000. Cdc42 is required for PIP(2)-induced actin polymerization and early development but not for cell viability. Curr Biol 10:758-765.
94. Yang L, Wang L, Zheng Y. 2006. Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts. Mol Biol Cell 17:4675-4685.
95. Czuchra A, Wu X, Meyer H, van Hengel J, Schroeder T, et al. 2005. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells. Mol Biol Cell 16:4473-4484.
96. Cappello S, Attardo A, Wu X, Iwasato T, ltohara S, et al. 2006. The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface. Nat Neurosci 9:1099-1107.
97. Snapper SB, Rosen FS, Mizoguchi E, Cohen P, Khan W, et al. 1998. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9:81-91.
98. Zhang H, Schaff UY, Green CE, Chen H, Sarantos MR, et al. 2006. Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils. Immunity 25:285-295.
99. Calle Y, Jones GE, Jagger C, Fuller K, Blundell MP, et al. 2004. WASp deficiency in mice results in failure to form osteoclast sealing zones and defects in bone resorption. Blood 103:3552-3561.
100. Li S, Wang Q, Chakladar A, Bronson RT, Bernards A. 2000. Gastric hyperplasia in mice lacking the putative Cdc42 effector IQG AP1. Mol Cell Biol 20:697-701.