CDC42 and PIP2 bind WASL, activating it

Stable Identifier
R-HSA-3928601
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Neural Wiskott-Aldrich syndrome protein (WASL, N-WASP) is a scaffold protein that transduces signals from cell surface receptors to the activation of the ARP2/3 complex and actin polymerization. N-WASP possesses a central GTPase binding domain (GBD) and an NH2-terminal WASP homology domain 1 (WH1). Adjacent to this is a basic region (B) and a C-terminal containing 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, N-WASP is maintained in an auto-inhibition state via interaction of the N-terminal GBD and the C-terminal VCA domains. This prevents access of the ARP2/3 complex to the VCA region. Activated CDC42 binds to the GBD region in N-WASP and this interaction releases the VCA region from auto-inhibition enabling binding of the ARP2/3 complex stimulating actin polymerization (Kim et al. 2000, Park & Cox 2009). Phosphoinositides (PtdIns(4,5)P2) interact with the basic (B) region in WASP and this interaction is important for activation of the WASP and ARP2/3 complex (Higgs & Pollard 2000).

Literature References
PubMed ID Title Journal Year
10995436 Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate

Rohatgi, R, Ho, HY, Kirschner, MW

J Cell Biol 2000
10219243 The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly

Rohatgi, R, Ma, L, Miki, H, Lopez, M, Kirchhausen, Tomas, Takenawa, T, Kirschner, MW

Cell 1999
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Orthologous Events
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