Wiskott-Aldrich Syndrome Protein Family: A family of microfilament proteins whose name derives from the fact that mutations in members of this protein family have been associated with WISKOTT-ALDRICH SYNDROME. They are involved in ACTIN polymerization and contain a polyproline-rich region that binds to PROFILIN, and a verprolin homology domain that binds G-ACTIN.Wiskott-Aldrich Syndrome Protein: WASP protein is mutated in WISKOTT-ALDRICH SYNDROME and is expressed primarily in hematopoietic cells. It is the founding member of the WASP protein family and interacts with CDC42 PROTEIN to help regulate ACTIN polymerization.Wiskott-Aldrich Syndrome: A rare, X-linked immunodeficiency syndrome characterized by ECZEMA; LYMPHOPENIA; and, recurrent pyogenic infection. It is seen exclusively in young boys. Typically, IMMUNOGLOBULIN M levels are low and IMMUNOGLOBULIN A and IMMUNOGLOBULIN E levels are elevated. Lymphoreticular malignancies are common.Wiskott-Aldrich Syndrome Protein, Neuronal: A member of the Wiskott-Aldrich syndrome protein family that is found at high levels in NERVE CELLS. It interacts with GRB2 ADAPTOR PROTEIN and with CDC42 PROTEIN.Actin-Related Protein 2: A PROFILIN binding domain protein that is part of the Arp2-3 complex. It is related in sequence and structure to ACTIN and binds ATP.Actin-Related Protein 3: A component of the Arp2-3 complex that is related in sequence and structure to ACTIN and that binds ATP. It is expressed at higher levels than ARP2 PROTEIN and does not contain a PROFILIN binding domain.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Actin-Related Protein 2-3 Complex: A complex of seven proteins including ARP2 PROTEIN and ARP3 PROTEIN that plays an essential role in maintenance and assembly of the CYTOSKELETON. Arp2-3 complex binds WASP PROTEIN and existing ACTIN FILAMENTS, and it nucleates the formation of new branch point filaments.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

*  Structure, function and regulation of WASH actin regulatory complex - Da Jia, Ph.D. - Rosen Lab - UT Southwestern Medical...
WASH is a recently discovered member of the Wiskott-Aldrich Syndrome Protein (WASP) family, which stimulates Arp2/3-mediated ...
  http://www.utsouthwestern.edu/labs/rosen/about/da-jia.html
*  WASF1 - Wiskott-Aldrich syndrome protein family member 1 - Homo sapiens (Human) - WASF1 gene & protein
Wiskott-Aldrich syndrome protein family member 1Add BLAST. 559. Amino acid modifications. Feature key. Position(s). Description ... sp,Q92558,WASF1_HUMAN Wiskott-Aldrich syndrome protein family member 1 OS=Homo sapiens OX=9606 GN=WASF1 PE=1 SV=1 ... "Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex.". ... "Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex.". ...
  http://www.uniprot.org/uniprot/Q92558
*  Retraction Note to: Clinical significance and expression of the PRSS3 and Wiskott-Aldrich syndrome protein family verprolin...
Clinical significance and expression of the PRSS3 and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 ...
  https://rd.springer.com/article/10.1007/s13277-016-5482-3
*  Wiskott-Aldrich syndrome protein family member 1
The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role ... HCA RNA Cell Line for Wiskott-Aldrich syndrome protein family member 1. ... Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple ... non-motor actin binding protein. *Wiskott-Aldrich syndrome protein family member 1 ...
  https://pharos.nih.gov/idg/targets/WASF1
*  Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma...
... and proteins of the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein (WAVE) family are involved in the ... Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma ... Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma ... Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma ...
  http://clincancerres.aacrjournals.org/content/12/8/2449
*  Abi-1-bridged tyrosine phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates...
Wiskott-Aldrich syndrome protein family member 2; WT, wild-type ... proteins are the homologues of Drosophila Ena. In Drosophila, ... monomer red fluorescent protein 1; PFA, paraformaldehyde; PKA, protein kinase A; PP, poly-proline; PRD, proline-rich domain; ... In the present study we have identified VASP, another member of the Mena/VASP family, as an Abi-1-bridged substrate of Abl. ... Ena is a substrate of the tyrosine kinase DAbl (Drosophila Abl). However, the link between Abl and the Mena/VASP family is not ...
  http://www.biochemj.org/content/441/3/889
*  Over-expression of WAVE3 activates NFκB signaling.(A) | Open-i
Western blot analysis of WAVE3-GFP protein levels in GFP and GFP-W3-expressing cells. (B) Luciferase-base ... Wiskott-Aldrich Syndrome Protein Family/biosynthesis/genetics*. Minor. *Extracellular Matrix/genetics/metabolism ... The WAVE3 cytoskeletal protein promotes cancer invasion and metastasis. We have shown that the WAVE3-mediated activation of ... pone-0110627-g002: Over-expression of WAVE3 activates NFκB signaling.(A) Western blot analysis of WAVE3-GFP protein levels in ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC4199728_pone.0110627.g002&req=4
*  Nap1 and WAVE1 are required for OL-pc function. (A) Con | Open-i
Wiskott-Aldrich Syndrome Protein Family/metabolism. Related in: MedlinePlus. © Copyright Policy Related In: Results - ... In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly ... In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly ... OL-protocadherin (OL-pc) is a transmembrane protein belonging to the cadherin superfamily, which has been shown to accumulate ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC2483522_jcb1820395f06&req=4
*  The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit | JCB
ARPC1/Arc40 mediates the interaction of the actin-related protein 2 and 3 complex with Wiskott-Aldrich syndrome protein family ... and separating 40 µg of protein by SDS-PAGE. Proteins were transferred onto PVDF membranes, blocked in 5% BSA, and probed with ... Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex. Nat. Cell Biol. 3:76-82. doi:10.1038/35050590. ... B) Immunoblot of proteins in anti-HA immune complexes shows coprecipitation of endogenous ARPC1 with recombinant Arp2 WT and ...
  http://jcb.rupress.org/content/208/2/161
*  WASF3 - Wikipedia
Wiskott-Aldrich syndrome protein family member 3 is a protein that in humans is encoded by the WASF3 gene. This gene encodes a ... member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that ... Millard TH, Machesky LM (2001). "The Wiskott-Aldrich syndrome protein (WASP) family". Trends Biochem. Sci. 26 (3): 198-9. doi: ... "Entrez Gene: WASF3 WAS protein family, member 3". Jones GE (2000). "Cellular signaling in macrophage migration and chemotaxis ...
  https://en.wikipedia.org/wiki/WASF3
*  WASF2 - Wikipedia
Wiskott-Aldrich syndrome protein family member 2 is a protein that in humans is encoded by the WASF2 gene. This gene encodes a ... "Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of Wiskott-Aldrich syndrome protein (WASP) with WASP ... member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that ... Millard TH, Machesky LM (2001). "The Wiskott-Aldrich syndrome protein (WASP) family". Trends Biochem. Sci. 26 (3): 198-9. doi: ...
  https://en.wikipedia.org/wiki/WASF2
*  Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation |...
Invadopodia formation was shown to rely on the ubiquitous member of the Wiskott-Aldrich syndrome protein family (N-WASP) ( ... Mizutani, K., Miki, H., He, H., Maruta, H. and Takenawa, T. (2002). Essential role of neural Wiskott-Aldrich syndrome protein ... Previous work has shown that tyrosine phosphorylation of proteins by Src or Src-family tyrosine kinases (SFK) is required for ... Src-family kinase inhibitor; Sigma-Aldrich), 20 μM STI571 (Abl/Arg kinase inhibitor; kindly provided by Novartis Pharma AG) or ...
  http://jcs.biologists.org/content/121/3/369
*  WAVE2 is necessary for limiting gaps and promoting spre | Open-i
Wiskott-Aldrich Syndrome Protein Family/physiology. Related in: MedlinePlus. © Copyright Policy - creative-commons Related In: ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC4263454_4115fig4&req=4
*  KEGG SSDB Paralog Search Result: pon:100434013
pon:100437132 wiskott-Aldrich syndrome protein family m K05748 497 111 ( -) 31 0.311 103 -, pon:100439168 ring finger protein ... pon:100451640 predicted GPI-anchored protein 58 268 119 ( -) 33 0.300 150 -, pon:100453562 wiskott-Aldrich syndrome protein- ... pon:100171409 Wiskott-Aldrich syndrome like K05747 505 104 ( -) 30 0.303 99 -, pon:100433281 U1 small nuclear ribonucleoprotein ... pon:100172383 RNA binding motif protein 12 932 128 ( -) 35 0.309 136 -, pon:100174148 WAS protein family member 1 K05753 559 ...
  http://www.kegg.jp/ssdb-bin/ssdb_paralog?org_gene=pon:100434013
*  Microglial Amyloid- 1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1: Implications for the...
"Involvement of Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) and Rac1 in the phagocytosis of ... High-mobility group box protein 1 (HMGB1) is an abundant nonhistone chromosomal protein that is released from cells undergoing ... 42, and high mobility group box protein 1 (HMGB1), a chromosomal protein, inhibits phagocytosis. In the present study, we ... is derived from the amyloid precursor protein; two major forms of A. , that is, A. 1-40 (A. 40) and A. 1-42 (A. 42), exist. We ...
  https://www.hindawi.com/journals/ijad/2012/685739/
*  WASF1 monoclonal antibody, clone S91-36 (HRP) - (MAB11597) - Products - Abnova
The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role ... Wiskott-Aldrich syndrome protein family member 1,homology of dictyostelium scar 1,verprolin homology domain-containing protein ... Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple ... downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been ...
  http://www.abnova.com/products/products_detail.asp?catalog_id=MAB11597
*  C-terminal EH-domain-containing proteins: consensus for a role in endocytic trafficking, EH? | Journal of Cell Science
Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex. Biochem. J. 380, 1-17. ... The intersectin 2 adaptor links Wiskott Aldrich Syndrome protein (WASp)-mediated actin polymerization to T cell antigen ... All mammalian C-terminal EHD proteins contain a putative P-loop motif, an ATP/GTP-binding site found in Ras-family proteins, ... The few identifiable C-terminal EHD proteins in other species are orthologs of the human C-terminal EHD protein family. The EHD ...
  http://jcs.biologists.org/content/118/18/4093
*  WASP and SCAR/WAVE proteins: the drivers of actin assembly | Journal of Cell Science
Wiskott-Aldrich syndrome protein): family proteins and the Arp2/3 complex. Biochem. J. 380, 1-17. ... Members of the Wiskott-Aldrich syndrome protein (WASP) family were subsequently identified as the major regulators of the Arp2/ ... a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. ... The WASP family consists of two principal classes of protein - WASPs and SCAR/WAVEs. WASPs are named after Wiskott-Aldrich ...
  http://jcs.biologists.org/content/122/15/2575
*  WASL Gene - GeneCards | WASL Protein | WASL Antibody
Protein Coding), Wiskott-Aldrich Syndrome Like, including: function, proteins, disorders, pathways, orthologs, and expression. ... This gene encodes a member of the Wiskott-Aldrich syndrome (WAS) protein family. Wiskott-Aldrich syndrome proteins share ... Domains & Families for WASL Gene Gene Families for WASL Gene. HGNC:. *14 : Wiskott-Aldrich Syndrome protein family ... WASL (Wiskott-Aldrich Syndrome Like) is a Protein Coding gene. Diseases associated with WASL include Wiskott-Aldrich Syndrome ...
  http://www.genecards.org/cgi-bin/carddisp.pl?gene=WASL
*  Integration with WASPs | Science Signaling
Members of the WASP (Wiskott-Aldrich syndrome protein) family appear to integrate such signals and are thus subject to a ... Higgs, H.N., and Pollard, T.D. (2000) Activation by Cdc42 and PIP2 of Wiscott-Aldrich Syndrome protein (WASp) stimulates actin ... Still more is to come, as investigators factor in the association of WASP proteins with receptors, viral proteins, other ... Activation of WASP through the Rho family GTPase Cdc42 and interaction with phosphatidylinositol 4,5-bisphosphate (PIP2) ...
  http://stke.sciencemag.org/content/2000/51/tw2
*  Plus it
WAVE1, a member of the Wiskott-Aldrich syndrome protein family, also regulates actin dynamics and is the effector of synaptic ... protein trafficking, protein degradation, protein phosphorylation/dephosphorylation, and mRNA stability. The list of important ... protein/protein interactions, and protein synthesis/degradation. Intracellular signal transduction mediators represent ... AP1 is another transcriptional factor composed of proteins belonging to the c-Fos, c-Jun, ATF, and JDP families that regulate ...
  http://www.jneurosci.org/content/30/45/14987
*  WASF1 ELISA & Assay Kits
... protein WAVE-1 , verprolin homology domain-containing protein 1 , wiskott-Aldrich syndrome protein family member 1 , WASP ... The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role ... Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple ... WAS Protein Family, Member 3 ELISA Kits * WAS Protein Homolog Associated with Actin, Golgi Membranes and Microtubules ELISA ...
  https://www.antibodies-online.com/rtk-signaling-pathway-8/wasf1-elisa-kit-1454/
*  The WASP and WAVE family proteins | Genome Biology | Full Text
The Wiskott-Aldrich syndrome protein (WASP) and WASP-family verprolin-homologous protein (WAVE) family proteins are fundamental ... Genetic studies using model organisms have also improved our understanding of how the WASP- and WAVE-family proteins act to ... The conserved function across species is to receive upstream signals from Rho-family small GTPases and send them to activate ... and cell biological studies have identified a wide array of regulatory molecules that bind to the WASP and WAVE proteins and ...
  https://genomebiology.biomedcentral.com/articles/10.1186/gb-2009-10-6-226
*  Gene Report for G00000037 - Genes2Cognition Neuroscience Research Programme
Wiskott-Aldrich syndrome protein family Verprolin-homologous protein), a downstream effector of IRSp53 that binds to the SH3 ... Neural Wiskott-Aldrich syndrome protein (N-WASP) functions in several intracellular events including filopodium formation, ... Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large- ... IRS-58 is a brain-enriched protein comprising at least four protein-protein interaction sites: a Cdc42Hs binding site, an Src ...
  http://www.genes2cognition.org/db/Gene/G00000037
*  anti-WASF1 antibody product blog
Immunogen: Recombinant Human Wiskott-Aldrich syndrome protein family member 1 protein (381-553AA). Conjugation: Non-conjugated ... Protein Family How To Order , Order Form , Protein Family , Contact Us , Log In ... CD278 Protein. • EBV EA Native Protein. • Hemoglobin Beta (HBb) ELISA Kit. • Thrombopoietin (TPO) ELISA Kit. more .... ... SALL4 Recombinant Protein. • Activin A (Activin-A) ELISA Kit. • IRAK Antibody. • Poly (ADP-ribose) glycohydrolase (PARG) ELISA ...
  http://pab.mybiosource.com/anti-wasf1-antibody_7053165

(1/222) Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex.

The Arp2/3 complex, a stable assembly of two actin-related proteins (Arp2 and Arp3) with five other subunits, caps the pointed end of actin filaments and nucleates actin polymerization with low efficiency. WASp and Scar are two similar proteins that bind the p21 subunit of the Arp2/3 complex, but their effect on the nucleation activity of the complex was not known. We report that full-length, recombinant human Scar protein, as well as N-terminally truncated Scar proteins, enhance nucleation by the Arp2/3 complex. By themselves, these proteins either have no effect or inhibit actin polymerization. The actin monomer-binding W domain and the p21-binding A domain from the C terminus of Scar are both required to activate Arp2/3 complex. A proline-rich domain in the middle of Scar enhances the activity of the W and A domains. Preincubating Scar and Arp2/3 complex with actin filaments overcomes the initial lag in polymerization, suggesting that efficient nucleation by the Arp2/3 complex requires assembly on the side of a preexisting filament-a dendritic nucleation mechanism. The Arp2/3 complex with full-length Scar, Scar containing P, W, and A domains, or Scar containing W and A domains overcomes inhibition of nucleation by the actin monomer-binding protein profilin, giving active nucleation over a low background of spontaneous nucleation. These results show that Scar and, likely, related proteins, such as the Cdc42 targets WASp and N-WASp, are endogenous activators of actin polymerization by the Arp2/3 complex.  (+info)

(2/222) The Arp2/3 complex is essential for the actin-based motility of Listeria monocytogenes.

Actin polymerisation is thought to drive the movement of eukaryotic cells and some intracellular pathogens such as Listeria monocytogenes. The Listeria surface protein ActA synergises with recruited host proteins to induce actin polymerisation, propelling the bacterium through the host cytoplasm [1]. The Arp2/3 complex is one recruited host factor [2] [3]; it is also believed to regulate actin dynamics in lamellipodia [4] [5]. The Arp2/3 complex promotes actin filament nucleation in vitro, which is further enhanced by ActA [6] [7]. The Arp2/3 complex also interacts with members of the Wiskott-Aldrich syndrome protein (WASP) [8] family - Scar1 [9] [10] and WASP itself [11]. We interfered with the targeting of the Arp2/3 complex to Listeria by using carboxy-terminal fragments of Scar1 that bind the Arp2/3 complex [11]. These fragments completely blocked actin tail formation and motility of Listeria, both in mouse brain extract and in Ptk2 cells overexpressing Scar1 constructs. In both systems, Listeria could initiate actin cloud formation, but tail formation was blocked. Full motility in vitro was restored by adding purified Arp2/3 complex. We conclude that the Arp2/3 complex is a host-cell factor essential for the actin-based motility of L. monocytogenes, suggesting that it plays a pivotal role in regulating the actin cytoskeleton.  (+info)

(3/222) Phosphorylation of WAVE downstream of mitogen-activated protein kinase signaling.

WAVE is a Wiskott-Aldrich syndrome protein (WASP)-family protein that functions in membrane-ruffling formation induced by Rac, a Rho family small GTPase. Here we report that WAVE is a phosphoprotein whose phosphorylation increases in response to various external stimuli that activate mitogen-activated protein (MAP) kinase signaling. When Swiss 3T3 cells are stimulated with platelet-derived growth factor, electrophoretic mobility shift occurs to WAVE, which reflects hyperphosphorylation. This is perfectly inhibited by the addition of PD98059, a specific inhibitor of MAP kinase kinase. Indeed, the ectopic expression of an activated mutant of MAP kinase kinase induces WAVE mobility shift. When MAP kinase activation is suppressed by PD98059, the intensity of platelet-derived growth factor-induced membrane ruffling is greatly reduced. In various cancer cell lines, the amount of WAVE mobility shift was found to increase significantly, suggesting the importance of WAVE hyperphosphorylation in the formation of membrane ruffles and oncogenic transformation.  (+info)

(4/222) Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold.

WAVE proteins are members of the Wiskott-Aldrich syndrome protein (WASP) family of scaffolding proteins that coordinate actin reorganization by coupling Rho-related small molecular weight GTPases to the mobilization of the Arp2/3 complex. We identified WAVE-1 in a screen for rat brain A kinase-anchoring proteins (AKAPs), which bind to the SH3 domain of the Abelson tyrosine kinase (Abl). Recombinant WAVE-1 interacts with cAMP-dependent protein kinase (PKA) and Abl kinases when expressed in HEK-293 cells, and both enzymes co-purify with endogenous WAVE from brain extracts. Mapping studies have defined binding sites for each kinase. Competition experiments suggest that the PKA-WAVE-1 interaction may be regulated by actin as the kinase binds to a site overlapping a verprolin homology region, which has been shown to interact with actin. Immunocytochemical analyses in Swiss 3T3 fibroblasts suggest that the WAVE-1 kinase scaffold is assembled dynamically as WAVE, PKA and Abl translocate to sites of actin reorganization in response to platelet-derived growth factor treatment. Thus, we propose a previously unrecognized function for WAVE-1 as an actin-associated scaffolding protein that recruits PKA and Abl.  (+info)

(5/222) Activation of the Arp2/3 complex by the Listeria acta protein. Acta binds two actin monomers and three subunits of the Arp2/3 complex.

ActA is a bacterially encoded protein that enables Listeria monocytogenes to hijack the host cell actin cytoskeleton. It promotes Arp2/3-dependent actin nucleation, but its interactions with cellular components of the nucleation machinery are not well understood. Here we show that two domains of ActA (residues 85-104 and 121-138) with sequence similarity to WASP homology 2 domains bind two actin monomers with submicromolar affinity. ActA binds Arp2/3 with a K(d) of 0.6 microm and competes for binding with the WASP family proteins N-WASP and Scar1. By chemical cross-linking, ActA, N-WASP, and Scar1 contact the same three subunits of the Arp2/3 complex, p40, Arp2, and Arp3. Interestingly, profilin competes with ActA for binding of Arp2/3, but actophorin (cofilin) does not. The minimal Arp2/3-binding site of ActA (residues 144-170) is C-terminal to both actin-binding sites and shares sequence homology with Arp2/3-binding regions of WASP family proteins. The maximal activity at saturating concentrations of ActA is identical to the most active domains of the WASP family proteins. We propose that ActA and endogenous WASP family proteins promote Arp2/3-dependent nucleation by similar mechanisms and require simultaneous binding of Arp2 and Arp3.  (+info)

(6/222) Two tandem verprolin homology domains are necessary for a strong activation of Arp2/3 complex-induced actin polymerization and induction of microspike formation by N-WASP.

All WASP family proteins share a common C terminus that consists of the verprolin homology domain (V), cofilin homology domain (C), and acidic region (A), through which they activate Arp2/3 complex-induced actin polymerization. In this study, we characterized the Arp2/3 complex-mediated actin polymerization activity of VCA fragments of all of the WASP family proteins: WASP, N-WASP, WAVE1, WAVE2, and WAVE3. All of the VCA fragments stimulated the nucleating activity of Arp2/3 complex. Among them, N-WASP VCA, which possesses two tandem V motifs, had a more potent activity than other VCA proteins. The chimeric protein experiments revealed that the V motif was more important to the activation potency than the CA region; two V motifs were required for full activity of N-WASP. COS7 cells overexpressing N-WASP form microspikes in response to epidermal growth factor. However, when a chimeric protein in which the VCA region of N-WASP is replaced with WAVE1 VCA was overexpressed, microspike formation was suppressed. Interestingly, when the N-WASP VCA region was replaced with WAVE1 VCA, having two V motifs, this chimeric protein could induce microspike formation. These results indicate that strong activation of Arp2/3 complex by N-WASP is mainly caused by its two tandem V motifs, which are essential for actin microspike formation.  (+info)

(7/222) Scar/WAVE is localised at the tips of protruding lamellipodia in living cells.

Cell motility entails the extension of cytoplasmic processes, termed lamellipodia and filopodia. Extension is driven by actin polymerisation at the tips of these processes via molecular complexes that remain to be characterised. We show here that a green fluorescent protein (GFP) fusion of the Wiskott-Aldrich syndrome protein family member Scar1/WAVE1 is specifically recruited to the tips of lamellipodia in living B16F1 melanoma cells. Scar1-GFP was recruited only to protruding lamellipodia and was absent from filopodia. The localisation of Scar was facilitated by the finding that the formerly described inhibition of lamellipodia formation by ectopical expression of Scar, could be overcome by the treatment of cells with aluminium fluoride. These findings show that Scar is strategically located at sites of actin polymerisation specifically engaged in the protrusion of lamellipodia.  (+info)

(8/222) N-WASP, WAVE and Mena play different roles in the organization of actin cytoskeleton in lamellipodia.

WASP- and Ena/VASP-family proteins have been reported to regulate the cortical actin cytoskeleton as downstream effectors of the Rho-family small G-proteins Rac and Cdc42, but their functions are little understood. We observed the localization of the WASP family proteins, N-WASP and WAVE, and the Ena/VASP family protein, Mena, in protruding lamellipodia. Rat fibroblast cell line 3Y1 protruded lamellipodia on poly-L-lysine-coated substrate without any trophic factor. N-WASP and Cdc42 were concentrated along the actin filament bundles of microspikes but not at the tips. By immunofluorescence and immunoelectron microscopy, both WAVE and Mena were observed to localize at the lamellipodium edge. Interestingly, Mena tended to concentrate at the microspike tips but WAVE did not. At the edge of the lamellipodium, the correlation between the fluorescence from Mena and actin filaments stained with the specific antibody and rhodamine-phalloidin, respectively, was much higher than that between WAVE and actin filament. The Ena/VASP homology 2 (EVH2) domain of avian Ena, an avian homolog of Mena, was localized to the lamellipodium edge and concentrated at the tip of microspikes. The SCAR homology domain (SHD) of human WAVE was distributed along the lamellipodium edge. These results indicate that N-WASP, WAVE and Mena have different roles in the regulation of the cortical actin cytoskeleton in the protruding lamellipodium. WAVE and Mena should be recruited to the lamellipodium edge through SHD and the EVH2 domain, respectively, to regulate the actin polymerization near the cell membrane. N-WASP should regulate the formation of the actin filament bundle in addition to activating Arp2/3 complex in lamellipodium under the control of Cdc42.  (+info)



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  • My family was planning to camp this weekend - the only possible campout for us this year - and now David and I are staying home. (blogspot.com)