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RHO GTPases Activate WASPs and WAVEs
Stable Identifier
R-HSA-5663213
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Signal Transduction (Homo sapiens)
Signaling by Rho GTPases, Miro GTPases and RHOBTB3 (Homo sapiens)
Signaling by Rho GTPases (Homo sapiens)
RHO GTPase Effectors (Homo sapiens)
RHO GTPases Activate WASPs and WAVEs (Homo sapiens)
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WASP and WAVE proteins belong to the Wiskott-Aldrich Syndrome protein family, with recessive mutations in the founding member WASP being responsible for the X-linked recessive immunodeficieny known as the Wiskott-Aldrich Syndrome. WASP proteins include WASP and WASL (N-WASP). WAVE proteins include WASF1 (WAVE1), WASF2 (WAVE2) and WASF3 (WAVE3). WASPs and WAVEs contain a VCA domain (consisting of WH2 and CA subdomains) at the C-terminus, responsible for binding to G-actin (WH2 subdomain) and the actin-associated ARP2/3 complex (CA subdomain). WASPs contain a WH1 (WASP homology 1) domain at the N-terminus, responsible for binding to WIPs (WASP-interacting proteins). A RHO GTPase binding domain (GBD) is located in the N-terminal half of WASPs and C-terminally located in WAVEs. RHO GTPases activate WASPs by disrupting the autoinhibitory interaction between the GBD and VCA domains, which allows WASPs to bind actin and the ARP2/3 complex and act as nucleation promoting factors in actin polymerization. WAVEs have the WAVE/SCAR homology domain (WHD/SHD) at the N-terminus, which binds ABI, NCKAP1, CYFIP2 and BRK1 to form the WAVE regulatory complex (WRC). Binding of the RAC1:GTP to the GBD of WAVEs most likely induces a conformational change in the WRC that allows activating phosphorylation of WAVEs by ABL1, thus enabling them to function as nucleation promoting factors in actin polymerization through binding G-actin and the ARP2/3 complex (Reviewed by Lane et al. 2014).
Literature References
PubMed ID
Title
Journal
Year
24969695
Structure and role of WASP and WAVE in Rho GTPase signalling in cancer
Jiang, WG
,
Martin, T
,
Weeks, HP
,
Lane, J
Cancer Genomics Proteomics
2014
Participants
Events
Activation of WASP and N-WASP by CDC42
(Homo sapiens)
WIP binds WASP,N-WASP, activating them
(Homo sapiens)
Src phosphorylate WASP,N-WASP
(Homo sapiens)
RAC1:GTP and PIP3 bind WAVE Regulatory Complex (WRC)
(Homo sapiens)
ABL phosphorylates WAVEs
(Homo sapiens)
p-ERK phosphorylates WAVEs and ABI
(Homo sapiens)
WASPs or WAVEs activate the ARP2/3 complex
(Homo sapiens)
(WASPs, WAVE):G-actin:ARP2/3 binds F-actin
(Homo sapiens)
Detachment of WASP/WAVE
(Homo sapiens)
Branching and elongation of mother and daughter filaments
(Homo sapiens)
Participates
as an event of
RHO GTPase Effectors (Homo sapiens)
Orthologous Events
RHO GTPases Activate WASPs and WAVEs (Bos taurus)
RHO GTPases Activate WASPs and WAVEs (Caenorhabditis elegans)
RHO GTPases Activate WASPs and WAVEs (Canis familiaris)
RHO GTPases Activate WASPs and WAVEs (Danio rerio)
RHO GTPases Activate WASPs and WAVEs (Dictyostelium discoideum)
RHO GTPases Activate WASPs and WAVEs (Drosophila melanogaster)
RHO GTPases Activate WASPs and WAVEs (Gallus gallus)
RHO GTPases Activate WASPs and WAVEs (Mus musculus)
RHO GTPases Activate WASPs and WAVEs (Rattus norvegicus)
RHO GTPases Activate WASPs and WAVEs (Saccharomyces cerevisiae)
RHO GTPases Activate WASPs and WAVEs (Schizosaccharomyces pombe)
RHO GTPases Activate WASPs and WAVEs (Sus scrofa)
RHO GTPases Activate WASPs and WAVEs (Xenopus tropicalis)
Cross References
BioModels Database
BIOMD0000000399
,
BIOMD0000000255
,
BIOMD0000000175
,
BIOMD0000000019
,
BIOMD0000000477
Authored
Orlic-Milacic, M (2014-10-24)
Rivero Crespo, F (2014-12-26)
Created
Orlic-Milacic, M (2015-01-16)
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