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

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

Locations in the PathwayBrowser

Expand all

Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Leishmania infection (Homo sapiens)
    - Parasite infection (Homo sapiens)
      - Leishmania phagocytosis (Homo sapiens)
        
        FCGR3A-mediated phagocytosis (Homo sapiens)
        
        CDC42:GTP binds PtdIns(4,5)P2:WASP,N-WASP (Homo sapiens)

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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).

Literature References

PubMed ID	Title	Journal	Year
10995437	Activation by Cdc42 and PIP(2) of Wiskott-Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex Higgs, HN, Pollard, TD	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
9883880	EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family Callebaut, I, Cossart, P, Dehoux, P	FEBS Lett	1998
10724160	Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein Kim, AS, Kakalis, LT, Abdul-Manan, N, Liu, GA, Rosen, MK	Nature	2000
19741094	Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP Park, H, Cox, D	Mol Biol Cell	2009
15452139	Regulation of WASP/WAVE proteins: making a long story short Bompard, G, Caron, E	J Cell Biol	2004

Participants

Input

Output

CDC42:GTP:WASP/N-WASP [plasma membrane] (Homo sapiens)

Participant Of

hasEvent

FCGR3A-mediated phagocytosis

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)