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The IQGAP-related protein DGAP1 mediates signaling to the actin cytoskeleton as an effector and a sequestrator of Rac1 GTPases

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Abstract

Proteins are typically categorized into protein families based on their domain organization. Yet, evolutionarily unrelated proteins can also be grouped together according to their common functional roles. Sequestering proteins constitute one such functional class, acting as macromolecular buffers and serving as an intracellular reservoir ready to release large quantities of bound proteins or other molecules upon appropriate stimulation. Another functional protein class comprises effector proteins, which constitute essential components of many intracellular signal transduction pathways. For instance, effectors of small GTP-hydrolases are activated upon binding a GTP-bound GTPase and thereupon participate in downstream interactions. Here we describe a member of the IQGAP family of scaffolding proteins, DGAP1 from Dictyostelium, which unifies the roles of an effector and a sequestrator in regard to the small GTPase Rac1. Unlike classical effectors, which bind their activators transiently leading to short-lived signaling complexes, interaction between DGAP1 and Rac1-GTP is stable and induces formation of a complex with actin-bundling proteins cortexillins at the back end of the cell. An oppositely localized Rac1 effector, the Scar/WAVE complex, promotes actin polymerization at the cell front. Competition between DGAP1 and Scar/WAVE for the common activator Rac1-GTP might provide the basis for the oscillatory re-polarization typically seen in randomly migrating Dictyostelium cells. We discuss the consequences of the dual roles exerted by DGAP1 and Rac1 in the regulation of cell motility and polarity, and propose that similar signaling mechanisms may be of general importance in regulating spatiotemporal dynamics of the actin cytoskeleton by small GTPases.

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References

  1. Birnbaumer L (1990) Transduction of receptor signal into modulation of effector activity by G proteins: the first 20 years or so. FASEB J 4:3178–3188

    CAS  PubMed  Google Scholar 

  2. MacLennan DH, Wong PT (1971) Isolation of a calcium-sequestering protein from sarcoplasmic reticulum. Proc Natl Acad Sci USA 68:1231–1235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Weber A (1999) Actin binding proteins that change extent and rate of actin monomer-polymer distribution by different mechanisms. Mol Cell Biochem 190:67–74

    Article  CAS  PubMed  Google Scholar 

  4. Buchler NE, Louis M (2008) Molecular titration and ultrasensitivity in regulatory networks. J Mol Biol 384:1106–1119

    Article  CAS  PubMed  Google Scholar 

  5. Weber A, Nachmias VT, Pennise CR, Pring M, Safer D (1992) Interaction of thymosin beta 4 with muscle and platelet actin: implications for actin sequestration in resting platelets. Biochemistry 31:6179–6185

    Article  CAS  PubMed  Google Scholar 

  6. Cao LG, Babcock GG, Rubenstein PA, Wang YL (1992) Effects of profilin and profilactin on actin structure and function in living cells. J Cell Biol 117:1023–1029

    Article  CAS  PubMed  Google Scholar 

  7. Curmi PA, Andersen SS, Lachkar S, Gavet O, Karsenti E, Knossow M, Sobel A (1997) The stathmin/tubulin interaction in vitro. J Biol Chem 272:25029–25036

    Article  CAS  PubMed  Google Scholar 

  8. Treves S, De Mattei M, Landfredi M, Villa A, Green NM, MacLennan DH, Meldolesi J, Pozzan T (1990) Calreticulin is a candidate for a calsequestrin-like function in Ca2+-storage compartments (calciosomes) of liver and brain. Biochem J 271:473–480

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Bustelo XR, Sauzeau V, Berenjeno IM (2007) GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo. Bioessays 29:356–370

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Colicelli J (2004) Human RAS superfamily proteins and related GTPases. Sci STKE 2004:RE13

  11. Cox AD, Der CJ (2010) Ras history: the saga continues. Small GTPases 1:2–27

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Faix J, Weber I, Mintert U, Köhler J, Lottspeich F, Marriott G (2001) Recruitment of cortexillin into the cleavage furrow is controlled by Rac1 and IQGAP-related proteins. EMBO J 20:3705–3715

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Novák B, Tyson JJ (2008) Design principles of biochemical oscillators. Nat Rev Mol Cell Biol 9:981–991

    Article  PubMed Central  PubMed  Google Scholar 

  16. Alon U (2007) An introduction to systems biology: design principles of biological circuits. Chapman & Hall/CRC, Boca Raton

    Google Scholar 

  17. Briggs MW, Sacks DB (2003) IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep 4:571–574

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Brandt DT, Grosse R (2007) Get to grips: steering local actin dynamics with IQGAPs. EMBO Rep 8:1019–1023

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. White CD, Erdemir HH, Sacks DB (2012) IQGAP1 and its binding proteins control diverse biological functions. Cell Signal 24:826–834

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Shannon KB (2012) IQGAP family members in yeast, Dictyostelium, and mammalian cells. Int J Cell Biol 2012:1–14

    Google Scholar 

  21. Vlahou G, Rivero F (2006) Rho GTPase signaling in Dictyostelium discoideum: insights from the genome. Eur J Cell Biol 85:947–959

    Article  CAS  PubMed  Google Scholar 

  22. Filić V, Marinović M, Faix J, Weber I (2012) A dual role for Rac1 GTPases in the regulation of cell motility. J Cell Sci 125:387–398

    Article  PubMed  Google Scholar 

  23. Miki H, Yamaguchi H, Suetsugu S, Takenawa T (2000) IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 408:732–735

    Article  CAS  PubMed  Google Scholar 

  24. Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418:790–793

    Article  CAS  PubMed  Google Scholar 

  25. Faix J, Steinmetz M, Boves H, Kammerer RA, Lottspeich F, Mintert U, Murphy J, Stock A, Aebi U, Gerisch G (1996) Cortexillins, major determinants of cell shape and size, are actin-bundling proteins with a parallel coiled-coil tail. Cell 86:631–642

    Article  CAS  PubMed  Google Scholar 

  26. Faix J, Clougherty C, Konzok A, Mintert U, Murphy J, Albrecht R, Mühlbauer B, Kuhlmann J (1998) The IQGAP-related protein DGAP1 interacts with Rac and is involved in the modulation of the F-actin cytoskeleton and control of cell motility. J Cell Sci 111:3059–3071

    CAS  PubMed  Google Scholar 

  27. Faix J, Dittrich W (1996) DGAP1, a homologue of rasGTPase activating proteins that controls growth, cytokinesis, and development in Dictyostelium discoideum. FEBS Lett 394:251–257

    Article  CAS  PubMed  Google Scholar 

  28. Vadlamudi RK, Li F, Barnes CJ, Bagheri-Yarmand R, Kumar R (2004) p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate. EMBO Rep 5:154–160

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Schwaller B (2010) Cytosolic Ca2+ buffers. Cold Spring Harb Perspect Biol 2:a004051

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. MacLennan DH, Reithmeier RA (1998) Ion tamers. Nat Struct Biol 5:409–411

    Article  CAS  PubMed  Google Scholar 

  31. Bolsover SR (2005) Calcium signalling in growth cone migration. Cell Calcium 37:395–402

    Article  CAS  PubMed  Google Scholar 

  32. Niggli E, Shirokova N (2007) A guide to sparkology: the taxonomy of elementary cellular Ca2+ signaling events. Cell Calcium 42:379–387

    Article  CAS  PubMed  Google Scholar 

  33. Moissoglu K, Slepchenko BM, Meller N, Horwitz AF, Schwartz MA (2006) In vivo dynamics of Rac-membrane interactions. Mol Biol Cell 17:2770–2779

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Berkovich R, Wolfenson H, Eisenberg S, Ehrlich M, Weiss M, Klafter J, Henis YI, Urbakh M (2011) Accurate quantification of diffusion and binding kinetics of non-integral membrane proteins by FRAP. Traffic 12:1648–1657

    Article  CAS  PubMed  Google Scholar 

  35. Sako Y, Hibino K, Miyauchi T, Miyamoto Y, Ueda M, Yanagida T (2000) Single-molecule imaging of signaling molecules in living cells. Single Mol 1:159–163

    Article  CAS  Google Scholar 

  36. Postma M, Bosgraaf L, Loovers HM, Van Haastert PJM (2004) Chemotaxis: signalling modules join hands at front and tail. EMBO Rep 5:35–40

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Reichl EM, Ren Y, Morphew MK, Delannoy M, Effler JC, Girard KD, Divi S, Iglesias PA, Kuo SC, Robinson DN (2008) Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr Biol 18:471–480

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Yumura S (2001) Myosin II dynamics and cortical flow during contractile ring formation in Dictyostelium cells. J Cell Biol 154:137–146

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Bretschneider T, Jonkman J, Köhler J, Medalia O, Barisic K, Weber I, Stelzer EHK, Baumeister W, Gerisch G (2002) Dynamic organization of the actin system in the motile cells of Dictyostelium. J Muscle Res Cell Motil 23:639–649

    Article  CAS  PubMed  Google Scholar 

  40. Weiner OD, Marganski WA, Wu LF, Altschuler SJ, Kirschner MW (2007) An actin-based wave generator organizes cell motility. PLoS Biol 5:2053–2063

    Article  CAS  Google Scholar 

  41. Lai FP, Szczodrak M, Block J, Faix J, Breitsprecher D, Mannherz HG, Stradal TE, Dunn GA, Small JV, Rottner K (2008) Arp2/3 complex interactions and actin network turnover in lamellipodia. EMBO J 27:982–992

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Diez S, Gerisch G, Anderson K, Müller-Taubenberger A, Bretschneider T (2005) Subsecond reorganization of the actin network in cell motility and chemotaxis. Proc Natl Acad Sci USA 102:7601–7606

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Medalia O, Weber I, Frangakis AS, Nicastro D, Gerisch G, Baumeister W (2002) Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography. Science 298:1209–1213

    Article  CAS  PubMed  Google Scholar 

  44. Urban E, Jacob S, Nemethova M, Resch GP, Small JV (2010) Electron tomography reveals unbranched networks of actin filaments in lamellipodia. Nat Cell Biol 12:429–435

    Article  CAS  PubMed  Google Scholar 

  45. Rotty JD, Wu C, Bear JE (2013) New insights into the regulation and cellular functions of the ARP2/3 complex. Nat Rev Mol Cell Biol 14:7–12

    Article  CAS  PubMed  Google Scholar 

  46. Small JV, Resch GP (2005) The comings and goings of actin: coupling protrusion and retraction in cell motility. Curr Opin Cell Biol 17:517–523

    Article  CAS  PubMed  Google Scholar 

  47. Weber I (2001) On the mechanism of cleavage furrow ingression in Dictyostelium. Cell Struct Funct 26:577–584

    Article  CAS  PubMed  Google Scholar 

  48. Weber I, Gerisch G, Heizer C, Murphy J, Badelt K, Stock A, Schwartz JM, Faix J (1999) Cytokinesis mediated through the recruitment of cortexillins into the cleavage furrow. EMBO J 18:586–594

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Insall R, Müller-Taubenberger A, Machesky L, Köhler J, Simmeth E, Atkinson SJ, Weber I, Gerisch G (2001) Dynamics of the Dictyostelium Arp2/3 complex in endocytosis, cytokinesis, and chemotaxis. Cell Motil Cytoskeleton 50:115–128

    Article  CAS  PubMed  Google Scholar 

  50. Pollitt AY, Insall RH (2008) Abi mutants in Dictyostelium reveal specific roles for the SCAR/WAVE complex in cytokinesis. Curr Biol 18:203–210

    Article  CAS  PubMed  Google Scholar 

  51. Garcia-Mata R, Boulter E, Burridge K (2011) The ‘invisible hand’: regulation of RHO GTPases by RHOGDIs. Nat Rev Mol Cell Biol 12:493–504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Kurella VB, Richard JM, Parke CL, LeCour LF, Bellamy HD, Worthylake DK (2009) Crystal structure of the GTPase-activating protein-related domain from IQGAP1. J Biol Chem 284:14857–14865

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Grohmanova K, Schlaepfer D, Hess D, Gutierrez P, Beck M, Kroschewski R (2004) Phosphorylation of IQGAP1 modulates its binding to Cdc42, revealing a new type of rho-GTPase regulator. J Biol Chem 279:48495–48504

    Article  CAS  PubMed  Google Scholar 

  54. Faix J, Weber I (2013) A dual role model for active Rac1 in cell migration. Small GTPases 4:110–115

    Article  PubMed Central  PubMed  Google Scholar 

  55. Xu J, Wang F, Van Keymeulen A, Herzmark P, Straight A, Kelly K, Takuwa Y, Sugimoto N, Mitchison T, Bourne HR (2003) Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114:201–214

    Article  CAS  PubMed  Google Scholar 

  56. Jilkine A, Marée AFM, Edelstein-Keshet L (2007) Mathematical model for spatial segregation of the Rho-family GTPases based on inhibitory crosstalk. Bull Math Biol 69:1943–1978

    Article  PubMed  Google Scholar 

  57. Narang A (2006) Spontaneous polarization in eukaryotic gradient sensing: a mathematical model based on mutual inhibition of frontness and backness pathways. J Theor Biol 240:538–553

    Article  CAS  PubMed  Google Scholar 

  58. Han JW, Leeper L, Rivero F, Chung CY (2006) Role of RacC for the regulation of WASP and phosphatidylinositol 3-kinase during chemotaxis of Dictyostelium. J Biol Chem 281:35224–35234

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Larochelle DA, Vithalani KK, De Lozanne A (1996) A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis. J Cell Biol 133:1321–1329

    Article  CAS  PubMed  Google Scholar 

  60. Tuxworth RI, Cheetham JL, Machesky LM, Spiegelmann GB, Weeks G, Insall RH (1997) Dictyostelium RasG is required for normal motility and cytokinesis, but not growth. J Cell Biol 138:605–614

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Chubb JR, Wilkins A, Thomas GM, Insall RH (2000) The Dictyostelium RasS protein is required for macropinocytosis, phagocytosis and the control of cell movement. J Cell Sci 113:709–719

    CAS  PubMed  Google Scholar 

  62. Tkachenko E, Sabouri-Ghomi M, Pertz O, Kim C, Gutierrez E, Machacek M, Groisman A, Danuser G, Ginsberg MH (2011) Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells. Nat Cell Biol 13:660–667

    Article  PubMed Central  PubMed  Google Scholar 

  63. Killich T, Plath PJ, Wei X, Bultmann H, Rensing L, Vicker MG (1993) The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium cells are not random. J Cell Sci 106:1005–1013

    PubMed  Google Scholar 

  64. Shenderov AD, Sheetz MP (1997) Inversely correlated cycles in speed and turning in an ameba: an oscillatory model of cell locomotion. Biophys J 72:2382–2389

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Weber I (2006) Is there a pilot in a pseudopod? Eur J Cell Biol 85:915–924

    Article  CAS  PubMed  Google Scholar 

  66. Otsuji M, Terashima Y, Ishihara S, Kuroda S, Matsushima K (2010) A conceptual molecular network for chemotactic behaviors characterized by feedback of molecules cycling between the membrane and the cytosol. Sci Signal 3:ra89

    Article  CAS  PubMed  Google Scholar 

  67. Tyson JJ, Chen KC, Novak B (2003) Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr Opin Cell Biol 15:221–231

    Article  CAS  PubMed  Google Scholar 

  68. Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, Safer D, Nachmias VT, Pollard TD (1992) The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells. Mol Biol Cell 3:1015–1024

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Perelroizen I, Marchand JB, Blanchoin L, Didry D, Carlier MF (1994) Interaction of profilin with G-actin and poly(l-proline). Biochemistry 33:8472–8478

    Article  CAS  PubMed  Google Scholar 

  70. Yu FX, Lin SC, Morrison-Bogorad M, Atkinson MA, Yin HL (1993) Thymosin beta 10 and thymosin beta 4 are both actin monomer sequestering proteins. J Biol Chem 268:502–509

    CAS  PubMed  Google Scholar 

  71. Larsson N, Segerman B, Howell B, Fridell K, Cassimeris L, Gullberg M (1999) Op18/stathmin mediates multiple region-specific tubulin and microtubule-regulating activities. J Cell Biol 146:1289–1302

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Racchetti G, Papazafiri P, Volpe P, Meldolesi J (1994) Calstorin, a new Ca2+ binding protein of the microsome lumen which is abundant in the rat brain. Biochem Biophys Res Commun 203:828–833

    Article  CAS  PubMed  Google Scholar 

  73. Eberhard M, Erne P (1994) Calcium and magnesium binding to rat parvalbumin. Eur J Biochem 222:21–26

    Article  CAS  PubMed  Google Scholar 

  74. Nägerl UV, Novo D, Mody I, Vergara JL (2000) Binding kinetics of calbindin-D(28k) determined by flash photolysis of caged Ca2+. Biophys J 79:3009–3018

    Article  PubMed Central  PubMed  Google Scholar 

  75. Faas GC, Schwaller B, Vergara JL, Mody I (2007) Resolving the fast kinetics of cooperative binding: Ca2+ buffering by calretinin. PLoS Biol 5:e311

    Article  PubMed Central  PubMed  Google Scholar 

  76. Hemsath L, Dvorsky R, Fiegen D, Carlier M-F, Ahmadian MR (2005) An electrostatic steering mechanism of Cdc42 recognition by Wiskott-Aldrich syndrome proteins. Mol Cell 20:313–324

    Article  CAS  PubMed  Google Scholar 

  77. Sudhaharan T, Liu P, Foo YH, Bu W, Lim KB, Wohland T, Ahmed S (2009) Determination of in vivo dissociation constant, KD, of Cdc42-effector complexes in live mammalian cells using single wavelength fluorescence cross-correlation spectroscopy. J Biol Chem 284:13602–13609

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Owen D, Mott HR, Laue ED, Lowe PN (2000) Residues in Cdc42 that specify binding to individual crib effector proteins. Biochemistry 39:1243–1250

    Article  CAS  PubMed  Google Scholar 

  79. Buchwald G, Hostinova E, Rudolph MG, Kraemer A, Sickmann A, Meyer HE, Scheffzek K, Wittinghofer A (2001) Conformational switch and role of phosphorylation in PAK activation. Mol Cell Biol 21:5179–5189

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Thompson G, Owen D, Chalk PA, Lowe PN (1998) Delineation of the Cdc42/Rac-binding domain of p21-activated kinase. Biochemistry 37:7885–7891

    Article  CAS  PubMed  Google Scholar 

  81. Haeusler LC, Blumenstein L, Stege P, Dvorsky R, Ahmadian MR (2003) Comparative functional analysis of the Rac GTPases. FEBS Lett 555:556–560

    Article  CAS  PubMed  Google Scholar 

  82. Fiegen D, Haeusler L-C, Blumenstein L, Herbrand U, Dvorsky R, Vetter IR, Ahmadian MR (2004) Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase. J Biol Chem 279:4743–4749

    Article  CAS  PubMed  Google Scholar 

  83. Nisimoto Y, Freeman JL, Motalebi SA, Hirshberg M, Lambeth JD (1997) Rac binding to p67(phox). Structural basis for interactions of the Rac1 effector region and insert region with components of the respiratory burst oxidase. J Biol Chem 272:18834–18841

    Article  CAS  PubMed  Google Scholar 

  84. Elliott SF, Allen G, Timson DJ (2012) Biochemical analysis of the interactions of IQGAP1 C-terminal domain with CDC42. World J Biol Chem 3:53–60

    Article  PubMed Central  PubMed  Google Scholar 

  85. Owen D, Campbell LJ, Littlefield K, Evetts KA, Li Z, Sacks DB, Lowe PN, Mott HR (2008) The IQGAP1-Rac1 and IQGAP1-Cdc42 interactions: interfaces differ between the complexes. J Biol Chem 283:1692–1704

    Article  CAS  PubMed  Google Scholar 

  86. Shi X, Foo YH, Sudhaharan T, Chong S-W, Korzh V, Ahmed S, Wohland T (2009) Determination of dissociation constants in living zebrafish embryos with single wavelength fluorescence cross-correlation spectroscopy. Biophys J 97:678–686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Wohlgemuth S, Kiel C, Krämer A, Serrano L, Wittinghofer F, Herrmann C (2005) Recognizing and defining true Ras binding domains I: biochemical analysis. J Mol Biol 348:741–758

    Article  CAS  PubMed  Google Scholar 

  88. Gorman C, Skinner RH, Skelly JV, Neidle S, Lowe PN (1996) Equilibrium and kinetic measurements reveal rapidly reversible binding of Ras to Raf. J Biol Chem 271:6713–6719

    Article  CAS  PubMed  Google Scholar 

  89. Sydor JR, Engelhard M, Wittinghofer A, Goody RS, Herrmann C (1998) Transient kinetic studies on the interaction of Ras and the Ras-binding domain of c-Raf-1 reveal rapid equilibration of the complex. Biochemistry 37:14292–14299

    Article  CAS  PubMed  Google Scholar 

  90. Linnemann T, Geyer M, Jaitner BK, Block C, Kalbitzer HR, Wittinghofer A, Herrmann C (1999) Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras subfamily. J Biol Chem 274:13556–13562

    Article  CAS  PubMed  Google Scholar 

  91. Linnemann T, Kiel C, Herter P, Herrmann C (2002) The activation of RalGDS can be achieved independently of its Ras binding domain. implications of an activation mechanism in Ras effector specificity and signal distribution. J Biol Chem 277:7831–7837

    Article  CAS  PubMed  Google Scholar 

  92. Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL (2000) Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase γ. Cell 103:931–944

    Article  CAS  PubMed  Google Scholar 

  93. Gronwald W, Huber F, Grünewald P, Spörner M, Wohlgemuth S, Herrmann C, Kalbitzer HR (2001) Solution structure of the Ras binding domain of the protein kinase Byr2 from Schizosaccharomyces pombe. Structure 9:1029–1041

    Article  CAS  PubMed  Google Scholar 

  94. Stieglitz B, Bee C, Schwarz D, Yildiz O, Moshnikova A, Khokhlatchev A, Herrmann C (2008) Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. EMBO J 27:1995–2005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the grant No. 098-0982913-2858 from Ministry of Science, Education and Sport of the Republic of Croatia to I. W. and a Grant from the Deutsche Forschungsgemeinschaft within the framework of German Research Council (DFG) priority programme (SPP1464) to J. F. V. F. was supported by the FP7-REGPOT-2012-2013-1 Grant Agreement Number 316289-InnoMol. We thank Dr. Marija-Mary Sopta for proofreading of the manuscript.

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  1. Division of Molecular Biology, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia

    Vedrana Filić, Maja Marinović & Igor Weber

  2. Hannover Medical School, Institute for Biophysical Chemistry, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Jan Faix

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  1. Vedrana Filić
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Filić, V., Marinović, M., Faix, J. et al. The IQGAP-related protein DGAP1 mediates signaling to the actin cytoskeleton as an effector and a sequestrator of Rac1 GTPases. Cell. Mol. Life Sci. 71, 2775–2785 (2014). https://doi.org/10.1007/s00018-014-1606-3

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