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Molecular Basis for Rho GTPase Signaling Specificity

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Abstract

There is now considerable evidence for the involvement of aberrant Rho GTPase activation in breast cancer development. Like Ras, Rho GTPases function as signaling nodes regulated by diverse extracellular stimuli. Rho GTPase activation is facilitated by multiple regulatory proteins, in particular guanine nucleotide exchange factors (GEFs) such as Dbl family proteins. Activated Rho GTPases in turn interact with and regulate a spectrum of functionally diverse downstream effectors, initiating a network of cytoplasmic and nuclear signaling cascades. Thus, Rho GTPases represent points of signaling convergence as well as relay switches that disseminate signaling divergence. In this review, we highlight issues relating to the structural basis by which Dbl family GEFs facilitate signaling convergence and Rho GTPase activation, and how Rho GTPases promote signal dissemination through downstream effectors.

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References

  1. Downward J: Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3: 11–22, 2003

    Google Scholar 

  2. Cox AD, Der CJ: Ras family signaling: therapeutic targeting. Cancer Biol Ther 1: 599–606, 2002

    Google Scholar 

  3. Sahai E, Marshall CJ: RHO-GTPases and cancer. Nat Rev Cancer 2: 133–142, 2002

    Google Scholar 

  4. Boettner B, Van Aelst L: The role of Rho GTPases in disease development. Gene 286: 155–174, 2002

    Google Scholar 

  5. Karnoub AE, Der CJ: Rho family GTPases and cellular transformation. In: Marc Symons (ed) Signal Transduction: Rho-GTPases. Landes Biosciences Pub. Co., pp 165–186, 2003

  6. Fritz G, Just I, Kaina B: Rho GTPases are over-expressed in human tumors. Int J Cancer 81: 682–687, 1999

    Google Scholar 

  7. Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B: Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer 87: 635–644, 2002

    Google Scholar 

  8. van Golen KL, Davies S, Wu ZF, Wang Y, Bucana CD, Root H, Chandrasekharappa S, Strawderman M, Ethier SP, Merajver SD: A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the in-flammatory breast cancer phenotype. Clin Cancer Res 5: 2511–2519, 1999

    Google Scholar 

  9. van Golen KL, Wu ZF, Qiao XT, Bao L, Merajver SD: RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia 2: 418–425, 2000

    Google Scholar 

  10. Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG: Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc Natl Acad Sci USA 97: 185–189, 2000

    Google Scholar 

  11. Schnelzer A, Prechtel D, Knaus U, Dehne K, Gerhard M, Graeff H, Harbeck N, Schmitt M, Lengyel E: Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene 19: 3013–3020, 2000

    Google Scholar 

  12. Tao W, Pennica D, Xu L, Kalejta RF, Levine AJ: Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1. Genes Dev 15: 1796–1807, 2001

    Google Scholar 

  13. Hamaguchi M, Meth JL, von Klitzing C, Wei W, Esposito D, Rodgers L, Walsh T, Welcsh P, King MC, Wigler MH: DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci USA 99: 13647–13652, 2002

    Google Scholar 

  14. Yuan BZ, Zhou X, Durkin ME, Zimonjic DB, Gumundsdottir K, Eyfjord JE, Thorgeirsson SS, Popescu NC: DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity. Oncogene 22: 445–450, 2003

    Google Scholar 

  15. Keely PJ, Westwick JK, Whitehead IP, Der CJ, Parise LV: Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature 390: 632–636, 1997

    Google Scholar 

  16. Bouzahzah B, Albanese C, Ahmed F, Pixley F, Lisanti MP, Segall JD, Condeelis J, Joyce D, Minden A, Der CJ, Chan A, Symons M, Pestell RG: Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways. Mol Med 7: 816–830, 2001

    Google Scholar 

  17. Etienne-Manneville S, Hall A: Rho GTPases in cell biology. Nature 420: 629–635, 2002

    Google Scholar 

  18. Van Aelst L, D'souza-Schorey C: Rho GTPases and signaling networks. Genes Dev 11: 2295–2322, 1997

    Google Scholar 

  19. Aspenstrom P: Effectors for the Rho GTPases. Curr Opin Cell Biol 11: 95–102, 1999

    Google Scholar 

  20. Hall A: Rho GTPases and the actin cytoskeleton. Science 279: 509–514, 1998

    Google Scholar 

  21. Ridley A: Rho GTPases. Integrating integrin signaling. J Cell Biol 150: F107-F109, 2000

    Google Scholar 

  22. Wherlock M, Mellor H: The Rho GTPase family: a Racs to Wrchs story. J Cell Sci 115: 239–240, 2002

    Google Scholar 

  23. Fransson A, Ruusala A, Aspenstrom P: Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem 278: 6495–6502, 2003

    Google Scholar 

  24. Wittinghofer F: Ras signalling. Caught in the act of the switch-on. Nature 394: 317319–317320, 1998

    Google Scholar 

  25. Schmidt A, Hall A: Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev 16: 1587–1609, 2002

    Google Scholar 

  26. Zheng Y: Dbl family guanine nucleotide exchange factors. Trends Biochem Sci 26: 724–732, 2001

    Google Scholar 

  27. Eva A, Aaronson SA: Isolation of a new human oncogene from a diffuse B-cell lymphoma. Nature 316: 273–275, 1985

    Google Scholar 

  28. Cote JF, Vuori K: Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J Cell Sci 115: 4901–4913, 2002

    Google Scholar 

  29. Moon SY, Zheng Y: Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 13: 13–22, 2003

    Google Scholar 

  30. Boguski MS, McCormick F: Proteins regulating Ras and its relatives. Nature 366: 643–654, 1993

    Google Scholar 

  31. Lamarche N, Hall A: GAPs for rho-related GTPases. Trends Genet 10: 436–440, 1994

    Google Scholar 

  32. Olofsson B: Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal 11: 545–554, 1999

    Google Scholar 

  33. Fukumoto Y, Kaibuchi K, Hori Y, Fujioka H, Araki S, Ueda T, Kikuchi A, Takai Y: Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene 5: 1321–1328, 1990

    Google Scholar 

  34. Leonard D, Hart MJ, Platko JV, Eva A, Henzel W, Evans T, Cerione RA: The identification and characterization of a GDP-dissociation inhibitor (GDI) for the CDC42Hs protein. J Biol Chem 267: 22860–22868, 1992

    Google Scholar 

  35. Hart MJ, Maru Y, Leonard D, Witte ON, Evans T, Cerione RA: A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs. Science 258: 812–815, 1992

    Google Scholar 

  36. Nomanbhoy TK, Leonard DA, Manor D, Cerione RA: Investigation of the GTP-binding/GTPase cycle of Cdc42Hs using extrinsic reporter group fluorescence. Biochem 35: 4602–4608, 1996

    Google Scholar 

  37. Keep NH, Barnes M, Barsukov I, Badii R, Lian LY, Segal AW, Moody PC, Roberts GC: A modulator of rho family G proteins, rhoGDI, binds these G proteins via an immunoglobulin-like domain and a flexible N-terminal arm. Structure 5: 623–633, 1997

    Google Scholar 

  38. Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK: C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature 387: 814–819, 1997

    Google Scholar 

  39. Hoffman GR, Nassar N, Cerione RA: Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100: 345–356, 2000

    Google Scholar 

  40. Symons M, Settleman J: Rho family GTPases: more than simple switches. Trends Cell Biol 10: 415–419, 2000

    Google Scholar 

  41. Schmidt A, Hall A: Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev 16: 1587–1609, 2002

    Google Scholar 

  42. Lemmon MA, Ferguson KM, Abrams CS: Pleckstrin homology domains and the cytoskeleton. FEBS Lett 513: 71–76, 2002

    Google Scholar 

  43. Habets GG, Scholtes EH, Zuydgeest D, van der Kammen RA, Stam JC, Berns A, Collard JG: Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 77: 537–549, 1994

    Google Scholar 

  44. Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG: A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 375: 338–340, 1995

    Google Scholar 

  45. Olson MF, Pasteris NG, Gorski JL, Hall A: Faciogenital dysplasia protein (FGD1) and Vav, two related proteins required for normal embryonic development, are upstream regulators of Rho GTPases. Curr Biol 6: 1628–1633, 1996

    Google Scholar 

  46. Zheng Y, Glaven JA, Wu WJ, Cerione RA: Phosphatidylinositol 4,5-bisphosphate provides an alternative to guanine nucleotide exchange factors by stimulating the dissociation of GDP from Cdc42Hs. J Biol Chem 271: 23815–23819, 1996

    Google Scholar 

  47. Han J, Das B, Wei W, Aelst LV, Mosteller RD, Khosravi-Far R, Westwick JK, Der CJ, Broek D: Lck regulates Vav activation of members of the Rho family of GTPases. Mol Cell Biol 17: 1346–1353, 1997

    Google Scholar 

  48. Abe K, Rossman KL, Liu B, Ritola KD, Chiang D, Campbell SL, Burridge K, Der CJ: Vav2 is an activator of Cdc42, Rac1, and RhoA. J Biol Chem 275: 10141–10149, 2000

    Google Scholar 

  49. Liu X, Wang H, Eberstadt M, Schnuchel A, Olejniczak ET, Meadows RP, Schkeryantz JM, Janowick DA, Harlan JE, Harris EA, Staunton DE, Fesik SW: NMR structure and mutagenesis of the N-terminal Dbl homology domain of the nucleotide exchange factor Trio. Cell 95: 269–277, 1998

    Google Scholar 

  50. Aghazadeh B, Zhu K, Kubiseski TJ, Liu GA, Pawson T, Zheng Y, Rosen MK: Structure and mutagenesis of the Dbl homology domain. Nat Struct Biol 5: 1098–1107, 1998

    Google Scholar 

  51. Aghazadeh B, Lowry WE, Huang XY, Rosen MK: Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation. Cell 102: 625–633, 2000

    Google Scholar 

  52. Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J: Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein. Cell 95: 259–268, 1998

    Google Scholar 

  53. Worthylake DK, Rossman KL, Sondek J: Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature 408: 682–688, 2000

    Google Scholar 

  54. Rossman KL, Worthylake DK, Snyder JT, Siderovski DP, Campbell SL, Sondek J: A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange. EMBO J 21: 1315–1326, 2002

    Google Scholar 

  55. Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J: Structural basis for the selective activation of Rho GTPases by Dbl exchange factors. Nat Struct Biol 9: 468–475, 2002

    Google Scholar 

  56. Karnoub AE, Worthylake DK, Rossman KL, Pruitt WM, Campbell SL, Sondek J, Der CJ: Molecular basis for Rac1 recognition by guanine nucleotide exchange factors. Nat Struct Biol 8: 1037–1041, 2001

    Google Scholar 

  57. van den Berghe N, Cool RH, Wittinghofer A: Discriminatory residues in ras and rap for guanine nucleotide exchange factor recognition. J Biol Chem 274: 11078–11085, 1999

    Google Scholar 

  58. Gao Y, Xing J, Streuli M, Leto TL, Zheng Y: Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors. J Biol Chem 276: 47530–47541, 2001

    Google Scholar 

  59. ArthurWT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K: XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. J Biol Chem 277: 42964–42972, 2002

    Google Scholar 

  60. Feig LA: Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases. Nat Cell Biol 1: E25-E27, 1999

    Google Scholar 

  61. Davies SP, Reddy H, Caivano M, Cohen P: Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J 351: 95–105, 2000

    Google Scholar 

  62. Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, McCormick F, Francke U, Abo A: Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 84: 723–734, 1996

    Google Scholar 

  63. Cheng L, Rossman KL, Mahon GM, Worthylake DK, Korus M, Sondek J, Whitehead IP: RhoGEF specificity mutants im-plicate RhoA as a target for Dbs transforming activity. Mol Cell Biol 22: 6895–6905, 2002

    Google Scholar 

  64. Bishop AL, Hall A: Rho GTPases and their effector proteins. Biochem J 348(Pt 2): 241–255, 2000

    Google Scholar 

  65. Wittinghofer A, Nassar N: How Ras-related proteins talk to their effectors. Trends Biochem Sci 21: 488–491, 1996

    Google Scholar 

  66. 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 17: 1324–1335, 1997

    Google Scholar 

  67. Lapouge K, Smith SJ, Walker PA, Gamblin SJ, Smerdon SJ, Rittinger K: Structure of the TPR domain of p67phox in complex with Rac GTP. Mol Cell 6: 899–907, 2000

    Google Scholar 

  68. Maesaki R, Ihara K, Shimizu T, Kuroda S, Kaibuchi K, Hakoshima T: The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1.Mol Cell 4: 793–803, 1999

    Google Scholar 

  69. Self AJ, Paterson HF, Hall A: Different structural organization of Ras and Rho effector domains. Oncogene 8: 655–661, 1993

    Google Scholar 

  70. Diekmann D, Nobes CD, Burbelo PD, Abo A, Hall A: Rac GTPase interacts with GAPs and target proteins through multiple effector sites. EMBO J 14: 5297–5305, 1995

    Google Scholar 

  71. Fujisawa JL, Madaule P, Ishizaki T, Watanabe G, Bito H, Saito Y, Hall A, Narumiya S: Different regions of Rho determine Rho-selective binding of different classes of Rho target molecules. J Biol Chem 273: 18943–18949, 1998

    Google Scholar 

  72. Bae CD, Min DS, Fleming IN, Exton JH: Determination of interaction sites on the small G protein RhoA for phospholipase D. J Biol Chem 273: 11596–11604, 1998

    Google Scholar 

  73. Sahai E, Alberts AS, Treisman R: RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J 17: 1350–1361, 1998

    Google Scholar 

  74. Mott HR, Owen D, Nietlispach D, Lowe PN, Manser E, Lim L, Laue ED: Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. Nature 399: 384–388, 1999

    Google Scholar 

  75. Abdul-Manan N, Aghazadeh B, Liu GA, Majumdar A, Ouerfelli O, Siminovitch KA, Rosen MK: Structure of Cdc42 in complex with the GTPase-binding domain of the ‘Wiskott-Aldrich syndrome’ protein. Nature 399: 379–383, 1999

    Google Scholar 

  76. Morreale A, Venkatesan M, Mott HR, Owen D, Nietlispach D, Lowe PN, Laue ED: Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol 7: 384–388, 2000

    Google Scholar 

  77. Burbelo PD, Drechsel D, Hall A: A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. J Biol Chem 270: 29071–29074, 1995

    Google Scholar 

  78. Morreale A, Venkatesan M, Mott HR, Owen D, Nietlispach D, Lowe PN, Laue ED: Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol 7: 384–388, 2000

    Google Scholar 

  79. Valencia A, Chardin P, Wittinghofer A, Sander C: The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry 30: 4637–4648, 1991

    Google Scholar 

  80. Freeman JL, Abo A, Lambeth JD: Rac ‘Insert Region’ is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. J Biol Chem 271: 19794–19801, 1996

    Google Scholar 

  81. Nisimoto Y, Freeman JLR, Motalebi SA, Hirshberg M, Lambeth JD: Rac binding to p67phox. J Biol Chem 272: 18834–18841, 1997

    Google Scholar 

  82. Wu WJ, Leonard DA, Cerione RA, Manor D: Interaction between Cdc42Hs and RhoGDI is mediated through the Rho insert region. J Biol Chem 26153–26158, 1997

  83. Walker SJ, Brown HA: Specificity of Rho insert-mediated activation of phospholipase D1. J Biol Chem 277: 26260–26267, 2002

    Google Scholar 

  84. Wu WJ, Lin R, Cerione RA, Manor D: Transformation activity of Cdc42 requires a region unique to Rho-related proteins. J Biol Chem 273: 16655–16658, 1998

    Google Scholar 

  85. Zong H, Raman N, Mickelson-Young LA, Atkinson SJ, Quilliam LA: Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation. J Biol Chem 274: 4551–4560, 1999

    Google Scholar 

  86. Karnoub AE, Der CJ, Campbell SL: The insert region of Rac1 is essential for membrane ruffling but not cellular transformation. Mol Cell Biol 21: 2847–2857, 2001

    Google Scholar 

  87. Joneson T, Bar-Sagi D: A Rac1 effector site controlling mitogenesis through superoxide production. J Biol Chem 273: 17991–17994, 1998

    Google Scholar 

  88. Joneson T, Bar-Sagi D: Suppression of Ras-induced apoptosis by the Rac GTPase. Mol Cell Biol 19: 5892–5901, 1999

    Google Scholar 

  89. Zohar M, Teramoto H, Katz BZ, Yamada KM, Gutkind JS: Effector domain mutants of Rho dissociate cytoskeletal changes from nuclear signaling and cellular transformation. Oncogene 17: 991–998, 1998

    Google Scholar 

  90. Joneson T, McDonough M, Bar-Sagi D, Van Aelst L: RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase. Science 274: 1374–1376, 1996

    Google Scholar 

  91. Lamarche N, Tapon N, Stowers L, Burbelo PD, Aspenstrom P, Bridges T, Chant J, Hall A: Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade. Cell 87: 519–529, 1996

    Google Scholar 

  92. Sahai E, Alberts AS, Treisman R: RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J 17: 1350–1361, 1998

    Google Scholar 

  93. Khosravi-Far R, White MA, Westwick JK, Solski PA, Chrzanowska-Wodnicka M, Van Aelst L, Wigler MH, Der CJ: Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Mol Cell Biol 16: 3923–3933, 1996

    Google Scholar 

  94. Reeder MK, Serebriiskii IG, Golemis EA, Chernoff J: Analysis of small GTPase signaling pathways using p21-activated kinase mutants that selectively couple to Cdc42. J Biol Chem 276: 40606–40613, 2001

    Google Scholar 

  95. Zugaza JL, Lopez-Lago MA, Caloca MJ, Dosil M, Movilla N, Bustelo XR: Structural determinants for the biological activity of Vav proteins. J Biol Chem 277: 45377–45392, 2002

    Google Scholar 

  96. Buchsbaum RJ, Connolly BA, Feig LA: Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin. J Biol Chem 278: 18833–18841, 2003

    Google Scholar 

  97. Buchsbaum RJ, Connolly BA, Feig LA: Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for Molecular basis for Rho GTPase 71 the p38 mitogen-activated protein kinase cascade. Mol Cell Biol 22: 4073–4085, 2002

    Google Scholar 

  98. Zhou K, Wang Y, Gorski JL, Nomura N, Collard J, Bokoch GM: Guanine nucleotide exchange factors regulate specificity of downstream signaling from Rac and Cdc42. J Biol Chem 273: 16782–16786, 1998

    Google Scholar 

  99. Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA: Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nat Cell Biol 4: 639–647, 2002

    Google Scholar 

  100. Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS: Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol 4: 574–582, 2002

    Google Scholar 

  101. Gardiner EM, Pestonjamasp KN, Bohl BP, Chamberlain C, Hahn KM, Bokoch GM: Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr Biol 12: 2029–2034, 2002

    Google Scholar 

  102. Itoh RE, Kurokawa K, Ohba Y, Yoshizaki H, Mochizuki N, Matsuda M: Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol Cell Biol 22: 6582–6591, 2002

    Google Scholar 

  103. Kraynov VS, Chamberlain C, Bokoch GM, Schwartz MA, Slabaugh S, Hahn KM: Localized Rac activation dynamics visualized in living cells. Science 290: 333–337, 2000

    Google Scholar 

  104. Hirshberg M, Stockley RW, Dodson G, Webb MR: The crystal structure of human Rac1, a member of the Rho-family complexed with a GTP analogue. Nat Struct Biol 4: 147–152, 1997

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Antoine E. Karnoub & Channing J. Der

  2. Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Sharon L. Campbell

  3. Center for Oncology and Cell Biology, North Shore-LIJ Research Institute, Manhasset, NY, USA

    Marc Symons

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  1. Antoine E. Karnoub
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Karnoub, A.E., Symons, M., Campbell, S.L. et al. Molecular Basis for Rho GTPase Signaling Specificity. Breast Cancer Res Treat 84, 61–71 (2004). https://doi.org/10.1023/B:BREA.0000018427.84929.5c

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