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JNK3 binding to arrestin‐3 differentially affects recruitment of upstream MAP kinase kinases
Author(s) -
Zhan Xuanzhi,
Kaoud Tamer S,
Kook Seunghyi,
Dalby Kevin N.,
Gurevich Vsevold V.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1042.4
Subject(s) - kinase , phosphorylation , microbiology and biotechnology , chemistry , ask1 , g protein coupled receptor , receptor , mitogen activated protein kinase kinase , protein kinase a , biology , biochemistry
Non‐visual arrestins‐2 and‐3 interact with numerous GPCRs and dozens of non‐receptors partners, such as MAP kinases. Arrestin‐3 promotes JNK3 activation, scaffolding ASK1‐MKK4‐JNK3 cascade. Full activation of JNKs, unlike other MAP kinases, requires two upstream kinases, MKK4 and MKK7, and each preferentially phosphorylating a distinct site, tyrosine (MKK4) and theronine (MKK7). It remains unclear whether arrestin‐3 can promote the activation of JNK3 by MKK7. Using phospho‐Tyr and phospho‐Thr antibodies we found that arrestin‐3 promotes the phosphorylation of both Tyr and Thr within the T‐P‐Y motif in COS‐7 cells. We also found that arrestin‐3 directly binds MKK7 comparably to MKK4. The binding of JNK3 enhanced the association of arrestin‐3 with MKK4, while reduced the binding of MKK7. With pure proteins we show that arrestin‐3 scaffolds MKK7‐JNK3 module at higher concentration than MKK4‐JNK3 module. Arresint‐3 also facilitates JNK3 activation in COS‐7 cells over‐expressing either MKK4 or MKK7. This is the first evidence that arrestin‐3 promotes JNK3 phosphorylation by MKK7. The data suggest that JNK3 binding has opposite effect on arrestin‐3 interactions with MKK4 and MKK7. Support: NIH GM081756, GM077561 and EY011500 (VVG) and GM059802 and Welch Foundation Grant F‐1390 (KND).