JNK3 enzyme binding to arrestin-3 differentially affects the recruitment of upstream mitogen-activated protein (MAP) kinase kinases.

Zhan X, Kaoud TS, Kook S, Dalby KN, Gurevich VV
J Biol Chem. 2013 288 (40): 28535-47

PMID: 23960075 · PMCID: PMC3789954 · DOI:10.1074/jbc.M113.508085

Arrestin-3 was previously shown to bind JNK3α2, MKK4, and ASK1. However, full JNK3α2 activation requires phosphorylation by both MKK4 and MKK7. Using purified proteins we show that arrestin-3 directly interacts with MKK7 and promotes JNK3α2 phosphorylation by both MKK4 and MKK7 in vitro as well as in intact cells. The binding of JNK3α2 promotes an arrestin-3 interaction with MKK4 while reducing its binding to MKK7. Interestingly, the arrestin-3 concentration optimal for scaffolding the MKK7-JNK3α2 module is ∼10-fold higher than for the MKK4-JNK3α2 module. The data provide a mechanistic basis for arrestin-3-dependent activation of JNK3α2. The opposite effects of JNK3α2 on arrestin-3 interactions with MKK4 and MKK7 is the first demonstration that the kinase components in mammalian MAPK cascades regulate each other's interactions with a scaffold protein. The results show how signaling outcomes can be affected by the relative expression of scaffolding proteins and components of signaling cascades that they assemble.

MeSH Terms (13)

Animals Arrestins Binding, Competitive Chlorocebus aethiops COS Cells Humans MAP Kinase Kinase 4 MAP Kinase Kinase 7 Mice Mitogen-Activated Protein Kinase 10 Phosphorylation Protein Binding Substrate Specificity

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