p-ERK phosphorylates WAVEs and ABI

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R-HSA-2029469
Type
Reaction [transition]
Species
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
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
17202194 Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex

Nakanishi, O, Suetsugu, S, Yamazaki, D, Takenawa, T

J Biochem 2007
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
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Catalyst Activity
Title
protein serine/threonine kinase activity of p-T,Y MAPK dimers [cytosol]
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