RHO GTPases Activate WASPs and WAVEs

Stable Identifier
R-HSA-5663213
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
Summation

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 Cancer Genomics Proteomics 2014
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