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PDBsum entry 1ej5

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protein links
Blood clotting PDB id
1ej5
Jmol
Contents
Protein chain
107 a.a. *
* Residue conservation analysis
PDB id:
1ej5
Name: Blood clotting
Title: Solution structure of the autoinhibited conformation of wasp
Structure: Wiskott-aldrich syndrome protein. Chain: a. Synonym: wasp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: A.S.Kim,L.T.Kakalis,N.Abdul-Manan,G.A.Liu,M.K.Rosen
Key ref:
A.S.Kim et al. (2000). Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein. Nature, 404, 151-158. PubMed id: 10724160 DOI: 10.1038/35004513
Date:
29-Feb-00     Release date:   05-Apr-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P42768  (WASP_HUMAN) -  Wiskott-Aldrich syndrome protein
Seq:
Struc:
502 a.a.
107 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 35 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     positive regulation of Arp2/3 complex-mediated actin nucleation   2 terms 
  Biochemical function     actin binding     1 term  

 

 
DOI no: 10.1038/35004513 Nature 404:151-158 (2000)
PubMed id: 10724160  
 
 
Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.
A.S.Kim, L.T.Kakalis, N.Abdul-Manan, G.A.Liu, M.K.Rosen.
 
  ABSTRACT  
 
The Rho-family GTPase, Cdc42, can regulate the actin cytoskeleton through activation of Wiskott-Aldrich syndrome protein (WASP) family members. Activation relieves an autoinhibitory contact between the GTPase-binding domain and the carboxy-terminal region of WASP proteins. Here we report the autoinhibited structure of the GTPase-binding domain of WASP, which can be induced by the C-terminal region or by organic co-solvents. In the autoinhibited complex, intramolecular interactions with the GTPase-binding domain occlude residues of the C terminus that regulate the Arp2/3 actin-nucleating complex. Binding of Cdc42 to the GTPase-binding domain causes a dramatic conformational change, resulting in disruption of the hydrophobic core and release of the C terminus, enabling its interaction with the actin regulatory machinery. These data show that 'intrinsically unstructured' peptides such as the GTPase-binding domain of WASP can be induced into distinct structural and functional states depending on context.
 
  Selected figure(s)  
 
Figure 3.
Figure 3: Stereoviews of the best-fit superpositions of the backbone (N, Ca, C) atoms of the 20 final NMR structures of GBD2 in 5% TFE (a) and GBD4-C (b). Residues 230-249 in a, and 241-249, 480-492 and the (Gly-Gly-Ser)[2] linker in b are not defined by the NMR data, appear mobile in solution and have been omitted for clarity. Structural layers are coloured as in Fig. 1.
Figure 5.
Figure 5: Steric incompatibility of the autoinhibited and activated structures. a, Surface of GBD1 that contacts Cdc42 (d[C-C] < 4.5 ) in the GTPase complex. View is the opposite face of WASP to that shown in Fig. 4b. Backbone is shown as a yellow tube. Side chains from residues 246 to 276 that are part of the interface are red. b, Surface (blue) of layer 1 of GBD4-C that contacts layers 2 and 3 in the autoinhibited structure. View is of layer 1 observed from the core of the domain. Surface of atoms that also contact Cdc42 in the activated structure is superimposed in red. Backbone and side chains are represented as in a, with a similar orientation of 1. c,d, Structures of the GBD1-Cdc42-GMPPCP complex and GBD4-C, respectively, rotated 90 about a horizontal axis relative to Fig. 4b, c. a,b generated with GRASP44; c,d with Ribbons43.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 404, 151-158) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23212475 J.D.Rotty, C.Wu, and J.E.Bear (2012).
New insights into the regulation and cellular functions of the ARP2/3 complex.
  Nat Rev Mol Cell Biol, 14, 7.  
20182458 A.J.Thrasher, and S.O.Burns (2010).
WASP: a key immunological multitasker.
  Nat Rev Immunol, 10, 182-192.  
19863535 A.Shcherbina, J.Cooley, M.I.Lutskiy, C.Benarafa, G.E.Gilbert, and E.Remold-O'Donnell (2010).
WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signalling.
  Br J Haematol, 148, 416-427.  
20005866 C.B.McDonald, K.L.Seldeen, B.J.Deegan, V.Bhat, and A.Farooq (2010).
Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control.
  Arch Biochem Biophys, 494, 216-225.  
20154219 C.E.Hughes, A.Y.Pollitt, J.Mori, J.A.Eble, M.G.Tomlinson, J.H.Hartwig, C.A.O'Callaghan, K.Fütterer, and S.P.Watson (2010).
CLEC-2 activates Syk through dimerization.
  Blood, 115, 2947-2955.  
20573979 D.M.Veltman, and R.H.Insall (2010).
WASP family proteins: their evolution and its physiological implications.
  Mol Biol Cell, 21, 2880-2893.  
20595519 E.Remold-O'Donnell (2010).
Lymphocytes with congenitally active WASP.
  Blood, 115, 5283-5284.  
20130240 H.Stabile, C.Carlino, C.Mazza, S.Giliani, S.Morrone, L.D.Notarangelo, L.D.Notarangelo, A.Santoni, and A.Gismondi (2010).
Impaired NK-cell migration in WAS/XLT patients: role of Cdc42/WASp pathway in the control of chemokine-induced beta2 integrin high-affinity state.
  Blood, 115, 2818-2826.  
20133692 J.Gureasko, O.Kuchment, D.L.Makino, H.Sondermann, D.Bar-Sagi, and J.Kuriyan (2010).
Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless.
  Proc Natl Acad Sci U S A, 107, 3430-3435.
PDB code: 3ksy
20513746 L.S.Westerberg, P.Meelu, M.Baptista, M.A.Eston, D.A.Adamovich, V.Cotta-de-Almeida, B.Seed, M.K.Rosen, P.Vandenberghe, A.J.Thrasher, C.Klein, F.W.Alt, and S.B.Snapper (2010).
Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes.
  J Exp Med, 207, 1145-1152.  
  20175130 S.N.Duleh, and M.D.Welch (2010).
WASH and the Arp2/3 complex regulate endosome shape and trafficking.
  Cytoskeleton (Hoboken), 67, 193-206.  
  20927343 T.Otomo, D.R.Tomchick, C.Otomo, M.Machius, and M.K.Rosen (2010).
Crystal structure of the Formin mDia1 in autoinhibited conformation.
  PLoS One, 5, 0.
PDB code: 3obv
21107423 Z.Chen, D.Borek, S.B.Padrick, T.S.Gomez, Z.Metlagel, A.M.Ismail, J.Umetani, D.D.Billadeau, Z.Otwinowski, and M.K.Rosen (2010).
Structure and control of the actin regulatory WAVE complex.
  Nature, 468, 533-538.
PDB code: 3p8c
19808890 A.Dovas, J.C.Gevrey, A.Grossi, H.Park, W.Abou-Kheir, and D.Cox (2009).
Regulation of podosome dynamics by WASp phosphorylation: implication in matrix degradation and chemotaxis in macrophages.
  J Cell Sci, 122, 3873-3882.  
19625501 A.Y.Pollitt, and R.H.Insall (2009).
WASP and SCAR/WAVE proteins: the drivers of actin assembly.
  J Cell Sci, 122, 2575-2578.  
19412530 B.Mészáros, I.Simon, and Z.Dosztányi (2009).
Prediction of protein binding regions in disordered proteins.
  PLoS Comput Biol, 5, e1000376.  
19379711 D.A.Adamovich, F.Nakamura, A.Worth, S.Burns, A.J.Thrasher, J.H.Hartwig, and S.B.Snapper (2009).
Activating mutations of N-WASP alter Shigella pathogenesis.
  Biochem Biophys Res Commun, 384, 284-289.  
19173579 D.P.LaLonde, and A.Bretscher (2009).
The scaffold protein PDZK1 undergoes a head-to-tail intramolecular association that negatively regulates its interaction with EBP50.
  Biochemistry, 48, 2261-2271.  
19217847 D.Van Valen, M.Haataja, and R.Phillips (2009).
Biochemistry on a leash: the roles of tether length and geometry in signal integration proteins.
  Biophys J, 96, 1275-1292.  
19259069 F.Marangoni, M.Bosticardo, S.Charrier, E.Draghici, M.Locci, S.Scaramuzza, C.Panaroni, M.Ponzoni, F.Sanvito, C.Doglioni, M.Liabeuf, B.Gjata, M.Montus, K.Siminovitch, A.Aiuti, L.Naldini, L.Dupré, M.G.Roncarolo, A.Galy, and A.Villa (2009).
Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models.
  Mol Ther, 17, 1073-1082.  
19628299 G.Bouma, S.O.Burns, and A.J.Thrasher (2009).
Wiskott-Aldrich Syndrome: Immunodeficiency resulting from defective cell migration and impaired immunostimulatory activation.
  Immunobiology, 214, 778-790.  
19917259 G.M.Rivera, D.Vasilescu, V.Papayannopoulos, W.A.Lim, and B.J.Mayer (2009).
A reciprocal interdependence between Nck and PI(4,5)P(2) promotes localized N-WASp-mediated actin polymerization in living cells.
  Mol Cell, 36, 525-535.  
19196002 G.Schreiber, G.Haran, and H.X.Zhou (2009).
Fundamental aspects of protein-protein association kinetics.
  Chem Rev, 109, 839-860.  
19082760 H.D.Ochs (2009).
Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes.
  Immunol Res, 44, 84-88.  
19741094 H.Park, and D.Cox (2009).
Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP.
  Mol Biol Cell, 20, 4500-4508.  
19487689 J.Zhang, X.Zhang, Y.Guo, L.Xu, and D.Pei (2009).
Sorting nexin 33 induces mammalian cell micronucleated phenotype and actin polymerization by interacting with Wiskott-Aldrich syndrome protein.
  J Biol Chem, 284, 21659-21669.  
19561083 M.Cammer, J.C.Gevrey, M.Lorenz, A.Dovas, J.Condeelis, and D.Cox (2009).
The mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo: a role for phosphatidylinositol 3-kinase and Cdc42.
  J Biol Chem, 284, 23302-23311.  
19165719 M.K.Yoon, V.Venkatachalam, A.Huang, B.S.Choi, C.M.Stultz, and J.J.Chou (2009).
Residual structure within the disordered C-terminal segment of p21(Waf1/Cip1/Sdi1) and its implications for molecular recognition.
  Protein Sci, 18, 337-347.  
19643989 M.Mani, S.Venkatasubrahmanyam, M.Sanyal, S.Levy, A.Butte, K.Weinberg, and T.Jahn (2009).
Wiskott-Aldrich syndrome protein is an effector of Kit signaling.
  Blood, 114, 2900-2908.  
19805221 M.P.Blundell, G.Bouma, J.Metelo, A.Worth, Y.Calle, L.A.Cowell, L.S.Westerberg, D.A.Moulding, S.Mirando, C.Kinnon, G.O.Cory, G.E.Jones, S.B.Snapper, S.O.Burns, and A.J.Thrasher (2009).
Phosphorylation of WASp is a key regulator of activity and stability in vivo.
  Proc Natl Acad Sci U S A, 106, 15738-15743.  
19874150 R.Dominguez (2009).
Actin filament nucleation and elongation factors--structure-function relationships.
  Crit Rev Biochem Mol Biol, 44, 351-366.  
19176514 S.H.Soderling (2009).
Grab your partner with both hands: cytoskeletal remodeling by Arp2/3 signaling.
  Sci Signal, 2, pe5.  
19589182 S.Kurisu, and T.Takenawa (2009).
The WASP and WAVE family proteins.
  Genome Biol, 10, 226.  
19956695 S.Liu, T.Okada, A.Assmann, J.Soto, C.W.Liew, H.Bugger, O.S.Shirihai, E.D.Abel, and R.N.Kulkarni (2009).
Insulin signaling regulates mitochondrial function in pancreatic beta-cells.
  PLoS One, 4, e7983.  
19759284 W.D.Bradley, and A.J.Koleske (2009).
Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts.
  J Cell Sci, 122, 3441-3454.  
19956793 C.M.Johnson, and W.Rodgers (2008).
Spatial Segregation of Phosphatidylinositol 4,5-Bisphosphate (PIP(2)) Signaling in Immune Cell Functions.
  Immunol Endocr Metab Agents Med Chem, 8, 349-357.  
18728185 D.W.Leung, C.Otomo, J.Chory, and M.K.Rosen (2008).
Genetically encoded photoswitching of actin assembly through the Cdc42-WASP-Arp2/3 complex pathway.
  Proc Natl Acad Sci U S A, 105, 12797-12802.  
18650809 H.C.Cheng, B.M.Skehan, K.G.Campellone, J.M.Leong, and M.K.Rosen (2008).
Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U).
  Nature, 454, 1009-1013.
PDB code: 2k42
18974829 K.G.Campellone, H.C.Cheng, D.Robbins, A.D.Siripala, E.J.McGhie, R.D.Hayward, M.D.Welch, M.K.Rosen, V.Koronakis, and J.M.Leong (2008).
Repetitive N-WASP-binding elements of the enterohemorrhagic Escherichia coli effector EspF(U) synergistically activate actin assembly.
  PLoS Pathog, 4, e1000191.  
18614018 K.G.Campellone, N.J.Webb, E.A.Znameroski, and M.D.Welch (2008).
WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER to Golgi transport.
  Cell, 134, 148-161.  
18689885 M.A.Shakir, K.Jiang, E.C.Struckhoff, R.S.Demarco, F.B.Patel, M.C.Soto, and E.A.Lundquist (2008).
The Arp2/3 activators WAVE and WASP have distinct genetic interactions with Rac GTPases in Caenorhabditis elegans axon guidance.
  Genetics, 179, 1957-1971.  
18650806 N.A.Sallee, G.M.Rivera, J.E.Dueber, D.Vasilescu, R.D.Mullins, B.J.Mayer, and W.A.Lim (2008).
The pathogen protein EspF(U) hijacks actin polymerization using mimicry and multivalency.
  Nature, 454, 1005-1008.  
18995840 S.B.Padrick, H.C.Cheng, A.M.Ismail, S.C.Panchal, L.K.Doolittle, S.Kim, B.M.Skehan, J.Umetani, C.A.Brautigam, J.M.Leong, and M.K.Rosen (2008).
Hierarchical regulation of WASP/WAVE proteins.
  Mol Cell, 32, 426-438.  
18941507 S.L.Lai, T.H.Chan, M.J.Lin, W.P.Huang, S.W.Lou, and S.J.Lee (2008).
Diaphanous-related formin 2 and profilin I are required for gastrulation cell movements.
  PLoS ONE, 3, e3439.  
19000814 X.Luo, and H.Yu (2008).
Protein metamorphosis: the two-state behavior of Mad2.
  Structure, 16, 1616-1625.  
  18191793 Y.Leung, S.Ally, and M.B.Goldberg (2008).
Bacterial actin assembly requires toca-1 to relieve N-wasp autoinhibition.
  Cell Host Microbe, 3, 39-47.  
17515921 B.J.Yeh, R.J.Rutigliano, A.Deb, D.Bar-Sagi, and W.A.Lim (2007).
Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors.
  Nature, 447, 596-600.  
17085436 C.Le Clainche, D.Schlaepfer, A.Ferrari, M.Klingauf, K.Grohmanova, A.Veligodskiy, D.Didry, D.Le, C.Egile, M.F.Carlier, and R.Kroschewski (2007).
IQGAP1 stimulates actin assembly through the N-WASP-Arp2/3 pathway.
  J Biol Chem, 282, 426-435.  
17724125 D.A.Moulding, M.P.Blundell, D.G.Spiller, M.R.White, G.O.Cory, Y.Calle, H.Kempski, J.Sinclair, P.J.Ancliff, C.Kinnon, G.E.Jones, and A.J.Thrasher (2007).
Unregulated actin polymerization by WASp causes defects of mitosis and cytokinesis in X-linked neutropenia.
  J Exp Med, 204, 2213-2224.  
17314411 D.Caracino, C.Jones, M.Compton, and C.L.Saxe (2007).
The N-terminus of Dictyostelium Scar interacts with Abi and HSPC300 and is essential for proper regulation and function.
  Mol Biol Cell, 18, 1609-1620.  
17942688 J.Heuvingh, M.Franco, P.Chavrier, and C.Sykes (2007).
ARF1-mediated actin polymerization produces movement of artificial vesicles.
  Proc Natl Acad Sci U S A, 104, 16928-16933.  
18042453 J.P.DiNitto, A.Delprato, M.T.Gabe Lee, T.C.Cronin, S.Huang, A.Guilherme, M.P.Czech, and D.G.Lambright (2007).
Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors.
  Mol Cell, 28, 569-583.
PDB codes: 2r09 2r0d
17092940 L.Y.Bourguignon, K.Peyrollier, E.Gilad, and A.Brightman (2007).
Hyaluronan-CD44 interaction with neural Wiskott-Aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to beta-catenin nuclear translocation, transcriptional up-regulation, and cell migration in ovarian tumor cells.
  J Biol Chem, 282, 1265-1280.  
17329259 M.St-Jean, T.Izard, and J.Sygusch (2007).
A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein.
  J Biol Chem, 282, 14309-14315.
PDB codes: 2ot0 2ot1
17785506 P.P.Banerjee, R.Pandey, R.Zheng, M.M.Suhoski, L.Monaco-Shawver, and J.S.Orange (2007).
Cdc42-interacting protein-4 functionally links actin and microtubule networks at the cytolytic NK cell immunological synapse.
  J Exp Med, 204, 2305-2320.  
17289588 P.Sarkar, C.Reichman, T.Saleh, R.B.Birge, and C.G.Kalodimos (2007).
Proline cis-trans isomerization controls autoinhibition of a signaling protein.
  Mol Cell, 25, 413-426.  
17476322 R.Pinyol, A.Haeckel, A.Ritter, B.Qualmann, and M.M.Kessels (2007).
Regulation of N-WASP and the Arp2/3 complex by Abp1 controls neuronal morphology.
  PLoS ONE, 2, e400.  
17914055 S.Takahashi, and P.M.Pryciak (2007).
Identification of novel membrane-binding domains in multiple yeast Cdc42 effectors.
  Mol Biol Cell, 18, 4945-4956.  
17890224 S.Tsuboi, and J.Meerloo (2007).
Wiskott-Aldrich syndrome protein is a key regulator of the phagocytic cup formation in macrophages.
  J Biol Chem, 282, 34194-34203.  
  17312144 S.Tsuboi (2007).
Requirement for a complex of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein in podosome formation in macrophages.
  J Immunol, 178, 2987-2995.  
17322911 T.Pawson, and N.Warner (2007).
Oncogenic re-wiring of cellular signaling pathways.
  Oncogene, 26, 1268-1275.  
17183359 T.Takenawa, and S.Suetsugu (2007).
The WASP-WAVE protein network: connecting the membrane to the cytoskeleton.
  Nat Rev Mol Cell Biol, 8, 37-48.  
17711847 X.Dong, G.Patino-Lopez, F.Candotti, and S.Shaw (2007).
Structure-function analysis of the WIP role in T cell receptor-stimulated NFAT activation: evidence that WIP-WASP dissociation is not required and that the WIP NH2 terminus is inhibitory.
  J Biol Chem, 282, 30303-30310.  
16943183 A.Seth, C.Otomo, and M.K.Rosen (2006).
Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLalpha and mDia1.
  J Cell Biol, 174, 701-713.  
16293614 E.Torres, and M.K.Rosen (2006).
Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP.
  J Biol Chem, 281, 3513-3520.  
16317717 H.Ardern, E.Sandilands, L.M.Machesky, P.Timpson, M.C.Frame, and V.G.Brunton (2006).
Src-dependent phosphorylation of Scar1 promotes its association with the Arp2/3 complex.
  Cell Motil Cytoskeleton, 63, 6.  
16613855 M.D.Hansen, and M.C.Beckerle (2006).
Opposing roles of zyxin/LPP ACTA repeats and the LIM domain region in cell-cell adhesion.
  J Biol Chem, 281, 16178-16188.  
16569662 P.A.Loomis, A.E.Kelly, L.Zheng, B.Changyaleket, G.Sekerková, E.Mugnaini, A.Ferreira, R.D.Mullins, and J.R.Bartles (2006).
Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to make actin bundles in cells.
  J Cell Sci, 119, 1655-1665.  
16582930 R.D.Hayward, J.M.Leong, V.Koronakis, and K.G.Campellone (2006).
Exploiting pathogenic Escherichia coli to model transmembrane receptor signalling.
  Nat Rev Microbiol, 4, 358-370.  
16582881 S.Tsuboi, S.Nonoyama, and H.D.Ochs (2006).
Wiskott-Aldrich syndrome protein is involved in alphaIIb beta3-mediated cell adhesion.
  EMBO Rep, 7, 506-511.  
16434392 T.Uruno, K.Remmert, and J.A.Hammer (2006).
CARMIL is a potent capping protein antagonist: identification of a conserved CARMIL domain that inhibits the activity of capping protein and uncaps capped actin filaments.
  J Biol Chem, 281, 10635-10650.  
16574661 Y.Yoo, X.Wu, C.Egile, R.Li, and J.L.Guan (2006).
Interaction of N-WASP with hnRNPK and its role in filopodia formation and cell spreading.
  J Biol Chem, 281, 15352-15360.  
15821030 D.W.Leung, and M.K.Rosen (2005).
The nucleotide switch in Cdc42 modulates coupling between the GTPase-binding and allosteric equilibria of Wiskott-Aldrich syndrome protein.
  Proc Natl Acad Sci U S A, 102, 5685-5690.  
16199863 E.A.Burton, T.N.Oliver, and A.M.Pendergast (2005).
Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway.
  Mol Cell Biol, 25, 8834-8843.  
15928485 H.D.Ochs, and L.D.Notarangelo (2005).
Structure and function of the Wiskott-Aldrich syndrome protein.
  Curr Opin Hematol, 12, 284-291.  
15826941 K.Sossey-Alaoui, X.Li, T.A.Ranalli, and J.K.Cowell (2005).
WAVE3-mediated cell migration and lamellipodia formation are regulated downstream of phosphatidylinositol 3-kinase.
  J Biol Chem, 280, 21748-21755.  
16264326 L.D.Notarangelo, L.D.Notarangelo, and H.D.Ochs (2005).
WASP and the phenotypic range associated with deficiency.
  Curr Opin Allergy Clin Immunol, 5, 485-490.  
16199520 L.M.Stamm, M.A.Pak, J.H.Morisaki, S.B.Snapper, K.Rottner, S.Lommel, and E.J.Brown (2005).
Role of the WASP family proteins for Mycobacterium marinum actin tail formation.
  Proc Natl Acad Sci U S A, 102, 14837-14842.  
16006560 M.A.Chellaiah (2005).
Regulation of actin ring formation by rho GTPases in osteoclasts.
  J Biol Chem, 280, 32930-32943.  
15570614 N.L.Delgado-Buenrostro, E.O.Hernández-González, M.Segura-Nieto, and A.Mújica (2005).
Actin polymerization in the equatorial and postacrosomal regions of guinea pig spermatozoa during the acrosome reaction is regulated by G proteins.
  Mol Reprod Dev, 70, 198-210.  
16257963 N.Yokoyama, J.Lougheed, and W.T.Miller (2005).
Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase.
  J Biol Chem, 280, 42219-42226.  
15596440 P.Moskwa, M.H.Paclet, M.C.Dagher, and E.Ligeti (2005).
Autoinhibition of p50 Rho GTPase-activating protein (GAP) is released by prenylated small GTPases.
  J Biol Chem, 280, 6716-6720.  
15728724 S.A.Myers, J.W.Han, Y.Lee, R.A.Firtel, and C.Y.Chung (2005).
A Dictyostelium homologue of WASP is required for polarized F-actin assembly during chemotaxis.
  Mol Biol Cell, 16, 2191-2206.  
15857951 V.Calabro, M.D.Daugherty, and A.D.Frankel (2005).
A single intermolecular contact mediates intramolecular stabilization of both RNA and protein.
  Proc Natl Acad Sci U S A, 102, 6849-6854.
PDB code: 1zbn
15997177 Y.Sasahara, and S.Tsuchiya (2005).
[Molecular pathogenesis of Wiskott-Aldrich syndrome]
  Nihon Rinsho Meneki Gakkai Kaishi, 28, 140-147.  
15283872 H.D.Ochs, and L.D.Notarangelo (2004).
X-linked immunodeficiencies.
  Curr Allergy Asthma Rep, 4, 339-348.  
15352163 J.R.Peterson, and E.A.Golemis (2004).
Autoinhibited proteins as promising drug targets.
  J Cell Biochem, 93, 68-73.  
15235593 J.R.Peterson, L.C.Bickford, D.Morgan, A.S.Kim, O.Ouerfelli, M.W.Kirschner, and M.K.Rosen (2004).
Chemical inhibition of N-WASP by stabilization of a native autoinhibited conformation.
  Nat Struct Mol Biol, 11, 747-755.
PDB code: 1t84
14707117 K.Badour, J.Zhang, F.Shi, Y.Leng, M.Collins, and K.A.Siminovitch (2004).
Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation.
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14732696 M.E.Ward, J.Y.Wu, and Y.Rao (2004).
Visualization of spatially and temporally regulated N-WASP activity during cytoskeletal reorganization in living cells.
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15169891 N.Martinez-Quiles, H.Y.Ho, M.W.Kirschner, N.Ramesh, and R.S.Geha (2004).
Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP.
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15362118 P.Sukumvanich, V.DesMarais, C.V.Sarmiento, Y.Wang, I.Ichetovkin, G.Mouneimne, S.Almo, and J.Condeelis (2004).
Cellular localization of activated N-WASP using a conformation-sensitive antibody.
  Cell Motil Cytoskeleton, 59, 141-152.  
14617808 S.Gasman, S.Chasserot-Golaz, M.Malacombe, M.Way, and M.F.Bader (2004).
Regulated exocytosis in neuroendocrine cells: a role for subplasmalemmal Cdc42/N-WASP-induced actin filaments.
  Mol Biol Cell, 15, 520-531.  
14676198 X.Wu, S.Suetsugu, L.A.Cooper, T.Takenawa, and J.L.Guan (2004).
Focal adhesion kinase regulation of N-WASP subcellular localization and function.
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15495215 Y.Calle, H.C.Chou, A.J.Thrasher, and G.E.Jones (2004).
Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells.
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15332112 Y.Le Page, F.Demay, and G.Salbert (2004).
A neural-specific splicing event generates an active form of the Wiskott-Aldrich syndrome protein.
  EMBO Rep, 5, 895-900.  
12853475 C.Yan, N.Martinez-Quiles, S.Eden, T.Shibata, F.Takeshima, R.Shinkura, Y.Fujiwara, R.Bronson, S.B.Snapper, M.W.Kirschner, R.Geha, F.S.Rosen, and F.W.Alt (2003).
WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.
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14514689 D.Owen, P.N.Lowe, D.Nietlispach, C.E.Brosnan, D.Y.Chirgadze, P.J.Parker, T.L.Blundell, and H.R.Mott (2003).
Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1).
  J Biol Chem, 278, 50578-50587.
PDB code: 1urf
14579346 E.Melamud, and J.Moult (2003).
Evaluation of disorder predictions in CASP5.
  Proteins, 53, 561-565.  
14512628 J.E.Dueber, B.J.Yeh, K.Chak, and W.A.Lim (2003).
Reprogramming control of an allosteric signaling switch through modular recombination.
  Science, 301, 1904-1908.  
12589062 J.Magdalena, T.H.Millard, S.Etienne-Manneville, S.Launay, H.K.Warwick, and L.M.Machesky (2003).
Involvement of the Arp2/3 complex and Scar2 in Golgi polarity in scratch wound models.
  Mol Biol Cell, 14, 670-684.  
14612666 K.Imai, S.Nonoyama, and H.D.Ochs (2003).
WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype.
  Curr Opin Allergy Clin Immunol, 3, 427-436.  
12655641 M.F.Carlier, C.Le Clainche, S.Wiesner, and D.Pantaloni (2003).
Actin-based motility: from molecules to movement.
  Bioessays, 25, 336-345.  
12872157 S.C.Panchal, D.A.Kaiser, E.Torres, T.D.Pollard, and M.K.Rosen (2003).
A conserved amphipathic helix in WASP/Scar proteins is essential for activation of Arp2/3 complex.
  Nat Struct Biol, 10, 591-598.  
12886288 S.E.Hitchcock-DeGregori (2003).
Now, swing your partner! 3D-domain switching of WASP activates Arp2/3 complex.
  Nat Struct Biol, 10, 583-584.  
12578964 S.H.Soderling, L.K.Langeberg, J.A.Soderling, S.M.Davee, R.Simerly, J.Raber, and J.D.Scott (2003).
Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice.
  Proc Natl Acad Sci U S A, 100, 1723-1728.  
12606577 S.M.Garrard, C.T.Capaldo, L.Gao, M.K.Rosen, I.G.Macara, and D.R.Tomchick (2003).
Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6.
  EMBO J, 22, 1125-1133.
PDB code: 1nf3
12700767 T.D.Pollard (2003).
The cytoskeleton, cellular motility and the reductionist agenda.
  Nature, 422, 741-745.  
  12727931 T.Wada, A.Konno, S.H.Schurman, E.K.Garabedian, S.M.Anderson, M.Kirby, D.L.Nelson, and F.Candotti (2003).
Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.
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12972601 V.Moreau, F.Tatin, C.Varon, and E.Génot (2003).
Actin can reorganize into podosomes in aortic endothelial cells, a process controlled by Cdc42 and RhoA.
  Mol Cell Biol, 23, 6809-6822.  
12429733 W.J.Smith, N.Nassar, A.Bretscher, R.A.Cerione, and P.A.Karplus (2003).
Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions.
  J Biol Chem, 278, 4949-4956.
PDB code: 1ni2
12209132 A.J.Thrasher (2002).
WASp in immune-system organization and function.
  Nat Rev Immunol, 2, 635-646.  
12006592 C.E.Alvarez, J.G.Sutcliffe, and E.A.Thomas (2002).
Novel isoform of insulin receptor substrate p53/p58 is generated by alternative splicing in the CRIB/SH3-binding region.
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11909959 D.Tian, V.Litvak, M.Toledo-Rodriguez, S.Carmon, and S.Lev (2002).
Nir2, a novel regulator of cell morphogenesis.
  Mol Cell Biol, 22, 2650-2662.  
12429845 D.Yarar, J.A.D'Alessio, R.L.Jeng, and M.D.Welch (2002).
Motility determinants in WASP family proteins.
  Mol Biol Cell, 13, 4045-4059.  
  12021239 F.Candotti, L.Notarangelo, R.Visconti, and J.O'Shea (2002).
Molecular aspects of primary immunodeficiencies: lessons from cytokine and other signaling pathways.
  J Clin Invest, 109, 1261-1269.  
12235133 G.O.Cory, R.Garg, R.Cramer, and A.J.Ridley (2002).
Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein.
  J Biol Chem, 277, 45115-45121.  
12029088 M.P.Scott, F.Zappacosta, E.Y.Kim, R.S.Annan, and W.T.Miller (2002).
Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1.
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11940652 R.E.Lamson, M.J.Winters, and P.M.Pryciak (2002).
Cdc42 regulation of kinase activity and signaling by the yeast p21-activated kinase Ste20.
  Mol Cell Biol, 22, 2939-2951.  
12147689 S.Benesch, S.Lommel, A.Steffen, T.E.Stradal, N.Scaplehorn, M.Way, J.Wehland, and K.Rottner (2002).
Phosphatidylinositol 4,5-biphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck, WIP, and Grb2.
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12181570 S.Eden, R.Rohatgi, A.V.Podtelejnikov, M.Mann, and M.W.Kirschner (2002).
Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.
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11470891 B.C.Lee, A.Pandit, P.A.Croonquist, and W.D.Hoff (2001).
Folding and signaling share the same pathway in a photoreceptor.
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11964736 D.M.Stewart, L.Tian, and D.L.Nelson (2001).
Linking cellular activation to cytoskeletal reorganization: Wiskott-Aldrich syndrome as a model.
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11238883 F.Bi, B.Debreceni, K.Zhu, B.Salani, A.Eva, and Y.Zheng (2001).
Autoinhibition mechanism of proto-Dbl.
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11598004 F.Castellano, C.Le Clainche, D.Patin, M.F.Carlier, and P.Chavrier (2001).
A WASp-VASP complex regulates actin polymerization at the plasma membrane.
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11438672 G.Buchwald, E.Hostinova, M.G.Rudolph, A.Kraemer, A.Sickmann, H.E.Meyer, K.Scheffzek, and A.Wittinghofer (2001).
Conformational switch and role of phosphorylation in PAK activation.
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11584266 G.Joberty, R.R.Perlungher, P.J.Sheffield, M.Kinoshita, M.Noda, T.Haystead, and I.G.Macara (2001).
Borg proteins control septin organization and are negatively regulated by Cdc42.
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11701921 I.R.Vetter, and A.Wittinghofer (2001).
The guanine nucleotide-binding switch in three dimensions.
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11553809 J.R.Peterson, R.S.Lokey, T.J.Mitchison, and M.W.Kirschner (2001).
A chemical inhibitor of N-WASP reveals a new mechanism for targeting protein interactions.
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11729265 M.B.Goldberg (2001).
Actin-based motility of intracellular microbial pathogens.
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11598009 O.Müller, D.I.Johnson, and A.Mayer (2001).
Cdc42p functions at the docking stage of yeast vacuole membrane fusion.
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11560487 R.Boujemaa-Paterski, E.Gouin, G.Hansen, S.Samarin, C.Le Clainche, D.Didry, P.Dehoux, P.Cossart, C.Kocks, M.F.Carlier, and D.Pantaloni (2001).
Listeria protein ActA mimics WASp family proteins: it activates filament barbed end branching by Arp2/3 complex.
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11584271 S.B.Snapper, F.Takeshima, I.Antón, C.H.Liu, S.M.Thomas, D.Nguyen, D.Dudley, H.Fraser, D.Purich, M.Lopez-Ilasaca, C.Klein, L.Davidson, R.Bronson, R.C.Mulligan, F.Southwick, R.Geha, M.B.Goldberg, F.S.Rosen, J.H.Hartwig, and F.W.Alt (2001).
N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.
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11892069 S.Nonoyama, and H.D.Ochs (2001).
Wiskott-Aldrich syndrome.
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10973991 C.Yang, M.Huang, J.DeBiasio, M.Pring, M.Joyce, H.Miki, T.Takenawa, and S.H.Zigmond (2000).
Profilin enhances Cdc42-induced nucleation of actin polymerization.
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10995437 H.N.Higgs, and T.D.Pollard (2000).
Activation by Cdc42 and PIP(2) of Wiskott-Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex.
  J Cell Biol, 150, 1311-1320.  
11052943 K.E.Prehoda, J.A.Scott, R.D.Mullins, and W.A.Lim (2000).
Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex.
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10938101 M.Jaquenoud, and M.Peter (2000).
Gic2p may link activated Cdc42p to components involved in actin polarization, including Bni1p and Bud6p (Aip3p).
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10995436 R.Rohatgi, H.Y.Ho, and M.W.Kirschner (2000).
Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate.
  J Cell Biol, 150, 1299-1310.  
10970852 R.S.Westphal, S.H.Soderling, N.M.Alto, L.K.Langeberg, and J.D.Scott (2000).
Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold.
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10995455 S.H.Zigmond (2000).
How WASP regulates actin polymerization.
  J Cell Biol, 150, F117-F120.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.