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PtdIns(4,5)P2 binds WASP, N-WASP
Stable Identifier
R-HSA-9670156
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
,
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
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Disease (Homo sapiens)
Infectious disease (Homo sapiens)
Parasitic Infection Pathways (Homo sapiens)
Leishmania infection (Homo sapiens)
Parasite infection (Homo sapiens)
Leishmania phagocytosis (Homo sapiens)
FCGR3A-mediated phagocytosis (Homo sapiens)
PtdIns(4,5)P2 binds WASP, N-WASP (Homo sapiens)
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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).
Literature References
PubMed ID
Title
Journal
Year
19955216
A Cdc42 activation cycle coordinated by PI 3-kinase during Fc receptor-mediated phagocytosis
Levinsohn, E
,
Mohan, S
,
Swanson, JA
,
Beemiller, P
,
Hoppe, AD
,
Gaeta, I
,
Zhang, Y
Mol Biol Cell
2010
Participants
Input
PI(4,5)P2 [plasma membrane]
WASP/N-WASP [cytosol]
(Homo sapiens)
Output
PI(4,5)P2:WASP/N-WASP [plasma membrane]
(Homo sapiens)
Participates
as an event of
FCGR3A-mediated phagocytosis (Homo sapiens)
Inferred From
Activation of WASP and N-WASP by CDC42 (Homo sapiens)
Authored
Murillo, JI (2019-12-05)
Reviewed
Gregory, DJ (2020-02-04)
Created
Murillo, JI (2019-12-05)
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