CDC42:GTP binds PtdIns(4,5)P2:WASP,N-WASP

Stable Identifier
R-HSA-9670155
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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CDC42:GTP binds PtdIns(4,5)P2:WASP,N-WASP
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Wiskott-Aldrich syndrome protein (WASP) and Neural-WASP (N-WASP, WASL) proteins are scaffolds that transduce signals from cell surface receptors to the activation of the ARP2/3 complex and actin polymerization. WASP and N-WASP possess a central GTPase binding domain (GBD) and an NH2-terminal WASP homology domain 1 (WH1) followed by a basic region (B), and a C-terminal VCA region that contains: a V domain (verprolin homology/WASP homology 2), a C domain (connecting), and an A motif (acidic). The VCA region is responsible for binding to and activating the ARP2/3 complex (Bompard & Caron 2004, Callebaut et al 1998). Under resting conditions, WASP and N-WASP are maintained in an autoinhibited state via interaction of the GBD and the VCA domains. This prevents access of the ARP2/3 complex and G-actin to the VCA region. Activated CDC42 binds to the GBD region of WASPs and this interaction releases the VCA region from autoinhibition, enabling binding of the ARP2/3 complex and stimulating actin polymerization (Kim et al 2000, Park & Cox 2009). Phosphoinositides (PtdIns(4,5)P2) interact with the basic (B) region in WASPs and this interaction is important for activation of the WASPs and the ARP2/3 complex (Higgs & Pollard 2000).
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Output
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Inferred From
Activation of WASP and N-WASP by CDC42 (Mus musculus)
Authored
Murillo, JI  (2019-12-05)
Reviewed
Gregory, DJ  (2020-02-04)
Created
Murillo, JI  (2019-12-05)
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