Analysis of the interaction between c-Jun and c-Jun N-terminal kinase in vivo

May, G. , Allen, K.E., Clark, W., Funk, M. and Gillespie, D.A. (1998) Analysis of the interaction between c-Jun and c-Jun N-terminal kinase in vivo. Journal of Biological Chemistry, 273(50), pp. 33429-33435. (doi: 10.1074/jbc.273.50.33429) (PMID:9837920)

Abstract

Regulation of c-Jun transcriptional activity is believed to depend on a physical interaction with c-Jun N-terminal kinase (JNK) that facilitates signal-regulated phosphorylation of multiple regulatory phosphoacceptor sites within the activation domain. Here we have investigated the structural requirements and consequences of regulatory phosphorylation for the interaction between c-Jun and JNK in vivo. We show that binding of JNK to c-Jun in vivo does not require JNK catalytic activity or the presence of the potential phosphoacceptor sites within c-Jun and that JNK retains the capacity to bind to a pseudo-phosphorylated mutant of c-Jun where these sites are replaced by phospho-mimetic aspartic acid residues. The c-Jun delta region docking site is essential for interaction with JNK in vivo but is not sufficient, because a c-Jun mutant that retains this region but that lacks the C-terminal DNA-binding domain fails to interact. Experiments using purified recombinant c-Jun and JNK proteins show that the c-Jun DNA-binding domain harbors an auxiliary interaction domain that has the potential to bind to JNK independently. Our results suggest that JNK can be tethered passively to c-Jun in situ through multiple interacting regions and, when activated, can stimulate c-Jun phosphorylation without necessarily dissociating from its substrate. Auxiliary interactions mediated by the DNA-binding domain could play a role in targeting JNK preferentially to c-Jun in specific homo- or heterodimeric complexes.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: May, Dr Gerhard
• Authors: May, G., Allen, K.E., Clark, W., Funk, M., and Gillespie, D.A.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry; Q Science > QH Natural history > QH426 Genetics
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Biological Chemistry
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X