2w2v › Citations

Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2.

Bunney TD, Opaleye O, Roe SM, Vatter P, Baxendale RW, Walliser C, Everett KL, Josephs MB, Christow C, Rodrigues-Lima F, Gierschik P, Pearl LH, Katan M
Mol Cell 34 223-33 (2009)
Related entries: 2w2t, 2w2w, 2w2x

Cited: 47 times
EuropePMC logo PMID: 19394299

Abstract

Rho family GTPases are important cellular switches and control a number of physiological functions. Understanding the molecular basis of interaction of these GTPases with their effectors is crucial in understanding their functions in the cell. Here we present the crystal structure of the complex of Rac2 bound to the split pleckstrin homology (spPH) domain of phospholipase C-gamma(2) (PLCgamma(2)). Based on this structure, we illustrate distinct requirements for PLCgamma(2) activation by Rac and EGF and generate Rac effector mutants that specifically block activation of PLCgamma(2), but not the related PLCbeta(2) isoform. Furthermore, in addition to the complex, we report the crystal structures of free spPH and Rac2 bound to GDP and GTPgammaS. These structures illustrate a mechanism of conformational switches that accompany formation of signaling active complexes and highlight the role of effector binding as a common feature of Rac and Cdc42 interactions with a variety of effectors.

Articles - 2w2v mentioned but not cited (2)

  1. Computational Equilibrium Thermodynamic and Kinetic Analysis of K-Ras Dimerization through an Effector Binding Surface Suggests Limited Functional Role. Sayyed-Ahmad A, Cho KJ, Hancock JF, Gorfe AA. J Phys Chem B 120 8547-8556 (2016)
  2. Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling. Walliser C, Tron K, Clauss K, Gutman O, Kobitski AY, Retlich M, Schade A, Röcker C, Henis YI, Nienhaus GU, Gierschik P. J. Biol. Chem. 290 17056-17072 (2015)


Reviews citing this publication (17)

  1. Phosphoinositides: tiny lipids with giant impact on cell regulation. Balla T. Physiol. Rev. 93 1019-1137 (2013)
  2. Mammalian phospholipase C. Kadamur G, Ross EM. Annu. Rev. Physiol. 75 127-154 (2013)
  3. PLC regulation: emerging pictures for molecular mechanisms. Bunney TD, Katan M. Trends Biochem. Sci. 36 88-96 (2011)
  4. Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions. Hota PK, Buck M. Cell. Mol. Life Sci. 69 3765-3805 (2012)
  5. One lipid, multiple functions: how various pools of PI(4,5)P(2) are created in the plasma membrane. Kwiatkowska K. Cell. Mol. Life Sci. 67 3927-3946 (2010)
  6. Pleckstrin homology (PH) like domains - versatile modules in protein-protein interaction platforms. Scheffzek K, Welti S. FEBS Lett. 586 2662-2673 (2012)
  7. The phospholipase C isozymes and their regulation. Gresset A, Sondek J, Harden TK. Subcell. Biochem. 58 61-94 (2012)
  8. Structures of Ras superfamily effector complexes: What have we learnt in two decades? Mott HR, Owen D. Crit. Rev. Biochem. Mol. Biol. 50 85-133 (2015)
  9. Dysfunction of phospholipase Cγ in immune disorders and cancer. Koss H, Bunney TD, Behjati S, Katan M. Trends Biochem. Sci. 39 603-611 (2014)
  10. Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors. Olson MF. Small GTPases 9 203-215 (2018)
  11. The Novel Functions of the PLC/PKC/PKD Signaling Axis in G Protein-Coupled Receptor-Mediated Chemotaxis of Neutrophils. Xu X, Jin T. J Immunol Res 2015 817604 (2015)
  12. TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation. Magno L, Bunney TD, Mead E, Svensson F, Bictash MN. Mol Neurodegener 16 22 (2021)
  13. The correlation between multidomain enzymes and multiple activation mechanisms--the case of phospholipase Cβ and its membrane interactions. Weinstein H, Scarlata S. Biochim. Biophys. Acta 1808 2940-2947 (2011)
  14. Not too little, not too much: the impact of mutation types in Wiskott-Aldrich syndrome and RAC2 patients. Hsu AP. Clin Exp Immunol 212 137-146 (2023)
  15. The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration. Jackson JT, Mulazzani E, Nutt SL, Masters SL. J Biol Chem 297 100905 (2021)
  16. Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets. Nizami S, Hall-Roberts H, Warrier S, Cowley SA, Di Daniel E. Br. J. Pharmacol. 176 3515-3532 (2019)
  17. Actin dynamics in cell migration. Schaks M, Giannone G, Rottner K. Essays Biochem. 63 483-495 (2019)

Articles citing this publication (28)

  1. Dynamin GTPase regulation is altered by PH domain mutations found in centronuclear myopathy patients. Kenniston JA, Lemmon MA. EMBO J. 29 3054-3067 (2010)
  2. Structural basis for the Rho- and phosphoinositide-dependent localization of the exocyst subunit Sec3. Yamashita M, Kurokawa K, Sato Y, Yamagata A, Mimura H, Yoshikawa A, Sato K, Nakano A, Fukai S. Nat. Struct. Mol. Biol. 17 180-186 (2010)
  3. Molecular basis of phosphatidylinositol 4-phosphate and ARF1 GTPase recognition by the FAPP1 pleckstrin homology (PH) domain. He J, Scott JL, Heroux A, Roy S, Lenoir M, Overduin M, Stahelin RV, Kutateladze TG. J. Biol. Chem. 286 18650-18657 (2011)
  4. Mechanism of phosphorylation-induced activation of phospholipase C-gamma isozymes. Gresset A, Hicks SN, Harden TK, Sondek J. J. Biol. Chem. 285 35836-35847 (2010)
  5. Characterization of phospholipase C gamma enzymes with gain-of-function mutations. Everett KL, Bunney TD, Yoon Y, Rodrigues-Lima F, Harris R, Driscoll PC, Abe K, Fuchs H, de Angelis MH, Yu P, Cho W, Katan M. J. Biol. Chem. 284 23083-23093 (2009)
  6. Phosphorylation of CSF-1R Y721 mediates its association with PI3K to regulate macrophage motility and enhancement of tumor cell invasion. Sampaio NG, Yu W, Cox D, Wyckoff J, Condeelis J, Stanley ER, Pixley FJ. J. Cell. Sci. 124 2021-2031 (2011)
  7. Structure-function study of the N-terminal domain of exocyst subunit Sec3. Baek K, Knödler A, Lee SH, Zhang X, Orlando K, Zhang J, Foskett TJ, Guo W, Dominguez R. J. Biol. Chem. 285 10424-10433 (2010)
  8. Structural and functional integration of the PLCγ interaction domains critical for regulatory mechanisms and signaling deregulation. Bunney TD, Esposito D, Mas-Droux C, Lamber E, Baxendale RW, Martins M, Cole A, Svergun D, Driscoll PC, Katan M. Structure 20 2062-2075 (2012)
  9. Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion. Timsah Z, Ahmed Z, Lin CC, Melo FA, Stagg LJ, Leonard PG, Jeyabal P, Berrout J, O'Neil RG, Bogdanov M, Ladbury JE. Nat. Struct. Mol. Biol. 21 180-188 (2014)
  10. Membrane environment exerts an important influence on rac-mediated activation of phospholipase Cγ2. Everett KL, Buehler A, Bunney TD, Margineanu A, Baxendale RW, Vatter P, Retlich M, Walliser C, Manning HB, Neil MA, Dunsby C, French PM, Gierschik P, Katan M. Mol. Cell. Biol. 31 1240-1251 (2011)
  11. Membrane curvature protein exhibits interdomain flexibility and binds a small GTPase. King GJ, Stöckli J, Hu SH, Winnen B, Duprez WG, Meoli CC, Junutula JR, Jarrott RJ, James DE, Whitten AE, Martin JL. J. Biol. Chem. 287 40996-41006 (2012)
  12. Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions. Bunney TD, Cole AR, Broncel M, Esposito D, Tate EW, Katan M. Structure 22 1831-1843 (2014)
  13. Cool-temperature-mediated activation of phospholipase C-γ2 in the human hereditary disease PLAID. Schade A, Walliser C, Wist M, Haas J, Vatter P, Kraus JM, Filingeri D, Havenith G, Kestler HA, Milner JD, Gierschik P. Cell. Signal. 28 1237-1251 (2016)
  14. Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model. Mahankali M, Alter G, Gomez-Cambronero J. Cell. Signal. 27 69-81 (2015)
  15. Noncatalytic Bruton's tyrosine kinase activates PLCγ2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells. Wist M, Meier L, Gutman O, Haas J, Endres S, Zhou Y, Rösler R, Wiese S, Stilgenbauer S, Hobeika E, Henis YI, Gierschik P, Walliser C. J Biol Chem 295 5717-5736 (2020)
  16. The molecular basis for immune dysregulation by the hyperactivated E62K mutant of the GTPase RAC2. Arrington ME, Temple B, Schaefer A, Campbell SL. J Biol Chem 295 12130-12142 (2020)
  17. A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency. Lagresle-Peyrou C, Olichon A, Sadek H, Roche P, Tardy C, Da Silva C, Garrigue A, Fischer A, Moshous D, Collette Y, Picard C, Casanova JL, André I, Cavazzana M. Haematologica 106 404-411 (2021)
  18. Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes. Siraliev-Perez E, Stariha JTB, Hoffmann RM, Temple BRS, Zhang Q, Hajicek N, Jenkins ML, Burke JE, Sondek J. Elife 11 e77809 (2022)
  19. Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer's disease. Tsai AP, Dong C, Lin PB, Oblak AL, Viana Di Prisco G, Wang N, Hajicek N, Carr AJ, Lendy EK, Hahn O, Atkins M, Foltz AG, Patel J, Xu G, Moutinho M, Sondek J, Zhang Q, Mesecar AD, Liu Y, Atwood BK, Wyss-Coray T, Nho K, Bissel SJ, Lamb BT, Landreth GE. Immunity 56 2121-2136.e6 (2023)
  20. Molecular mechanism of constitutively active Rab11A was revealed by crystal structure of Rab11A S20V. Choi JY, Shin YC, Yoon JH, Kim CM, Lee JH, Jeon JH, Park HH. FEBS Lett. 590 819-827 (2016)
  21. Overcoming Acquired Epigenetic Resistance to BTK Inhibitors. Shaffer AL, Phelan JD, Wang JQ, Huang D, Wright GW, Kasbekar M, Choi J, Young RM, Webster DE, Yang Y, Zhao H, Yu X, Xu W, Roulland S, Ceribelli M, Zhang X, Wilson KM, Chen L, McKnight C, Klumpp-Thomas C, Thomas CJ, Häupl B, Oellerich T, Rae Z, Kelly MC, Ahn IE, Sun C, Gaglione EM, Wilson WH, Wiestner A, Staudt LM. Blood Cancer Discov 2 630-647 (2021)
  22. Recurrent switch 2 domain RAC2 mutations in intravascular large B-cell lymphoma. Kodgule R, Chen J, Khonde P, Robinson J, D'Albora A, Cook L, Fronick CC, Fulton R, Srivatsan SN, Cimino PJ, Duncavage EJ. Blood Adv 6 6051-6055 (2022)
  23. The Conformational State of the BTK Substrate PLCγ Contributes to Ibrutinib Resistance. Joseph RE, Lowe J, Fulton DB, Engen JR, Wales TE, Andreotti AH. J Mol Biol 434 167422 (2022)
  24. Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling. Li W, Sano R, Apatira M, DeAnda F, Gururaja T, Yang M, Lundgaard G, Pan C, Liu J, Zhai Y, Yoon WH, Wang L, Tse C, Souers AJ, Lee CH. Mol Cancer Ther 23 35-46 (2024)
  25. Combined Immunodeficiency Caused by a Novel De Novo Gain-of-Function RAC2 Mutation. Zhang L, Chen Z, Li W, Liu Q, Wang Y, Chen X, Tian Z, Yang Q, An Y, Zhang Z, Mao H, Tang X, Lv G, Zhao X. J Clin Immunol 42 1280-1292 (2022)
  26. Computational and in vitro Pharmacodynamics Characterization of 1A-116 Rac1 Inhibitor: Relevance of Trp56 in Its Biological Activity. González N, Cardama GA, Chinestrad P, Robles-Valero J, Rodríguez-Fdez S, Lorenzo-Martín LF, Bustelo XR, Lorenzano Menna P, Gomez DE. Front Cell Dev Biol 8 240 (2020)
  27. Decreased conformational stability in the oncogenic N92I mutant of Ras-related C3 botulinum toxin substrate 1. Toyama Y, Kontani K, Katada T, Shimada I. Sci Adv 5 eaax1595 (2019)
  28. The Alzheimer's disease-associated protective Plcγ2-P522R variant promotes immune functions. Takalo M, Wittrahm R, Wefers B, Parhizkar S, Jokivarsi K, Kuulasmaa T, Mäkinen P, Martiskainen H, Wurst W, Xiang X, Marttinen M, Poutiainen P, Haapasalo A, Hiltunen M, Haass C. Mol Neurodegener 15 52 (2020)


Quick links