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Arrestin‐3 binding to JNK1alpha1/JNK2alpha2: modulation of JNK1 and JNK2 activity via scaffolding
Author(s) -
Kook Seunghyi,
Zhan Xuanzhi,
Kaoud Tamer S,
Dalby Kevin N,
Gurevich Vsevolod V,
Gurevich Eugenia 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.1042.6
Subject(s) - scaffold protein , phosphorylation , kinase , gene isoform , microbiology and biotechnology , mapk/erk pathway , arrestin , chemistry , mitogen activated protein kinase , signal transduction , biology , biochemistry , g protein coupled receptor , gene
Non‐visual arrestins scaffold mitogen‐activated protein kinase (MAPK) cascades, bringing together three components of MAPK signaling modules. The c‐Jun N‐terminal kinases (JNKs) are members of MAPK family and three JNKs isoforms (JNK1, JNK2, and JNK3) have been identified. JNK1 and JNK2 are ubiquitously expressed, whereas JNK3 is expressed mainly in testes and neuronal tissues. Arrestin‐3 isoform has been shown to enhance JNK3 activity by scaffolding JNK3 with upstream kinases. However, it has not been documented whether arrestin‐3 can modulate the activity of JNK1 and JNK2 isoforms. Using purified proteins we found that arrestin‐3 directly binds JNK1α1 and JNK2α2. Reconstitution of JNK1α1 or JNK2α2 signaling module with either MKK4 or MKK7 in the presence of different arrestin‐3 concentrations showed that arrestin‐3 acts as scaffold, facilitating JNK1α1 and JNK2α2 phosphorylation at optimal concentration. Arrestin‐3 also enhanced phosphorylation of endogenous JNK1 and 2 isoforms when upstream kinases MKK4 or MKK7 were overexpressed together with arrestin‐3 in COS‐7 cells. Thus, the data suggest that arrestin‐3 also modulates JNK1 and JNK2 activity in non‐neuronal cells acting as a scaffold for these JNK isoforms and upstream kinases. Support: NIH Grants NS065868 and DA030103 (EVG), GM077561, GM081756, and EY011500 (VVG), GM059802 and Welch Foundation Grant F‐1390 (KND).