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PMID: 24292834 Published · ppublish English Journal Article

Arrestin-dependent activation of JNK family kinases.

Handbook of experimental pharmacology ·Vol. 219 ·2014-00-00 ·Pages 259-80

Zhan X, Kook S, Gurevich EV, Gurevich VV

Abstract

The activity of all mitogen-activated protein kinases (MAPKs) is stimulated via phosphorylation by upstream MAPK kinases (MAPKK), which are in their turn activated via phosphorylation by MAPKK kinases (MAPKKKs). The cells ensure the specificity of signaling in these cascades by employing a variety of scaffolding proteins that bind matching MAPKKKs, MAPKKs, and MAPKs. All four vertebrate arrestin subtypes bind JNK3, but only arrestin-3 serves as a scaffold, promoting JNK3 activation in intact cells. Arrestin-3-mediated JNK3 activation does not depend on arrestin-3 interaction with G protein-coupled receptors (GPCRs), as demonstrated by the ability of some arrestin mutants that cannot bind receptors to activate JNK3, whereas certain mutants with enhanced GPCR binding fail to promote JNK3 activation. Recent findings suggest that arrestin-3 directly binds both MAPKKs necessary for JNK activation and facilitates JNK3 phosphorylation at both Thr (by MKK4) and Tyr (by MKK7). JNK3 is expressed in a limited set of cell types, whereas JNK1 and JNK2 isoforms are as ubiquitous as arrestin-3. Recent study showed that arrestin-3 facilitates the activation of JNK1 and JNK2, scaffolding MKK4/7-JNK1/2/3 signaling complexes. In all cases, arrestin-3 acts by bringing the kinases together: JNK phosphorylation shows biphasic dependence on arrestin-3, being enhanced at lower and suppressed at supraoptimal concentrations. Thus, arrestin-3 regulates the activity of multiple JNK isoforms, suggesting that it might play a role in survival and apoptosis of all cell types.

MeSH Terms
Animals Apoptosis/physiology Arrestins/metabolism Cell Survival/physiology Humans JNK Mitogen-Activated Protein Kinases/metabolism Mitogen-Activated Protein Kinase 10/metabolism Mitogen-Activated Protein Kinases/metabolism Phosphorylation/physiology Receptors, G-Protein-Coupled/metabolism
Chemicals
Arrestins Receptors, G-Protein-Coupled arrestin3 Mitogen-Activated Protein Kinase 10 JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhan Xuanzhi
Department of Pharmacology, Vanderbilt University, 2200 Pierce Avenue, Nashville, TN, 37232, USA, xuanzhi.zhan@vanderbilt.edu.
Kook Seunghyi
Gurevich Eugenia V
Gurevich Vsevolod V
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Article Info
Journal
Handbook of experimental pharmacology
Abbr.
Handb Exp Pharmacol
ISSN
0171-2004
DOI
10.1007/978-3-642-41199-1_13
Email
xuanzhi.zhan@vanderbilt.edu
Published
2014-00-00
Pages
259-80
Language
English
Region
Germany
NLM ID
7902231
PMCID
PMC4514028
Subset
IM
Grants
NEI NIH HHS · R01 EY011500 · United States
NIGMS NIH HHS · R01 GM077561 · United States
NINDS NIH HHS · R01 NS065868 · United States
NIDA NIH HHS · R13 DA037694 · United States
External Links
PubMed source DOI: 10.1007/978-3-642-41199-1_13 PMC Full Text
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