title: JNK3 enzyme binding to arrestin-3 differentially affects the recruitment of upstream mitogen-activated protein (MAP) kinase kinases.
abstract: 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.
authors: From the Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232 and.
authors: Xuanzhi
authors: X
authors: Zhan
authors: Tamer S
authors: TS
authors: Kaoud
authors: Seunghyi
authors: S
authors: Kook
authors: Kevin N
authors: KN
authors: Dalby
authors: Vsevolod V
authors: VV
authors: Gurevich
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D001667:Binding, Competitive; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D048688:MAP Kinase Kinase 7 / Q000378:metabolism*; D051379:Mice; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D019390:Arrestins; C082333:arrestin3; D048057:Mitogen-Activated Protein Kinase 10; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482559:MAP2K4 protein, human; C482570:Map2k7 protein, mouse
keywords: Arrestin; Cell Signaling; Jun N-terminal Kinase (JNK); MAP Kinases (MAPKs); Protein Kinases; Protein Phosphorylation
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