Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 459265, 9 pages
Review Article

Diverse Roles of JNK and MKK Pathways in the Brain

1Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
2Department of Molecular and Systems Neurobiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
3Global COE Program “Comprehensive Center of Education and Research for Chemical Biology of the Diseases”, University of Tokyo, Tokyo 113-0033, Japan

Received 11 August 2011; Accepted 1 November 2011

Academic Editor: M. Gaestel

Copyright © 2012 Tokiwa Yamasaki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The c-Jun NH2-terminal protein kinase (JNK) plays important roles in a broad range of physiological processes. JNK is controlled by two upstream regulators, mitogen-activated protein kinase kinase (MKK) 4 and MKK7, which are activated by various MAPKKKs. Studies employing knockout mice have demonstrated that the JNK signaling pathway is involved in diverse phenomena in the brain, regulating brain development and maintenance as well as animal metabolism and behavior. Furthermore, examination of single or combined knockout mice of Jnk1, Jnk2, and Jnk3 has revealed both functional differences and redundancy among JNK1, JNK2, and JNK3. Phenotypic differences between knockouts of MKK4 and MKK7 have also been observed, suggesting that the JNK signaling pathway in the brain has a complex nature and is intricately regulated. This paper summarizes the functional properties of the major JNK signaling components in the developing and adult brain.