Reactome | p-ERK phosphorylates WAVEs and ABI

p-ERK phosphorylates WAVEs and ABI

Stable Identifier

R-HSA-2029469

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
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        FCGR3A-mediated phagocytosis (Homo sapiens)
        
        p-ERK phosphorylates WAVEs and ABI (Homo sapiens)

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The ARP2/3 complex shows higher affinity for the phosphorylated VCA domain of WAVE2 than for the unphosphorylated VCA domain. WAVE proteins can be phosphorylated by various kinases. Active ERK (Mitogen activated protein kinase 3) phosphorylates the WAVE regulatory complex (WRC) on multiple serine/threonine sites within the proline-rich domains (PRDs) of WAVE2 and ABI1. Phosphorylation of the PRDs would disrupt their interaction with SH3 and PLP binding domains, potentially altering WRC activation. ERK phosphorylates both S343 and T346 in WAVE2 and S183, S216, S225, S392, and S410 in ABI1. Cumulatively, the phosphorylation of both WAVE2 and ABI in the WAVE regulatory complex (WRC) contributes to the RAC-induced WRC conformational change that exposes the VCA domain, leading to binding and activation of ARP2/3 (Mendoza et al. 2011, Nakanishi et al. 2007). ERK phosphorylation sites in WAVE2 are not strictly conserved in WAVE1 and WAVE3 but, based on the amino acid sequence, other potential ERK phosphorylation sites exist.

Literature References

PubMed ID	Title	Journal	Year
17202194	Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex Nakanishi, O, Suetsugu, S, Yamazaki, D, Takenawa, T	J Biochem	2007
21419341	ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex Mendoza, MC, Er, EE, Zhang, W, Ballif, BA, Elliott, HL, Danuser, G, Blenis, J	Mol Cell	2011
15657136	Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation Leng, Y, Zhang, J, Badour, K, Arpaia, E, Freeman, S, Cheung, P, Siu, M, Siminovitch, K	Proc Natl Acad Sci U S A	2005