The isoform-specific functions of the c-Jun N-terminal Kinases (JNKs): differences revealed by gene targeting.
The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family. In mammalian genomes, three genes encode the JNK family. To evaluate JNK function, mice have been created with deletions in one or more of three Jnk genes. Initial studies on jnk1(-/-) or jnk2(-/-) mice have shown roles for these JNKs in the immune system whereas studies on jnk3(-/-) mice have highlighted roles for JNK3 in the nervous system. Further studies have highlighted the contributions of JNK1 and/or JNK2 to a range of biological and pathological processes. These include bone remodelling and joint disease, inflammatory and autoimmune diseases, obesity, diabetes, cardiovascular disease, liver disease and tumorigenesis in addition to effects in neurons. These results emphasise the differences in the roles played by JNK isoforms in vivo and suggest that the design of JNK inhibitors for subsequent therapeutic uses may benefit from selective inhibition of individual JNK isoforms.
Bogoyevitch
Marie A
MA
Cell Signalling Laboratory, Biochemistry and Molecular Biology (M310), School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Western Australia, Australia. marieb@cyllene.uwa.edu.au
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009369:Neoplasms / Q000201:enzymology; D009420:Nervous System / Q000201:enzymology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D048031:JNK Mitogen-Activated Protein Kinases