Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 283, Issue 23, Pages 15903-15911Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M710006200
Keywords
-
Categories
Funding
- MRC [G0400620] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/C512302/1] Funding Source: researchfish
- Medical Research Council [G0400620] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/C512302/1] Funding Source: Medline
- Medical Research Council [G0400620] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
The c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway mediates stress responses in cells. JNK activity is regulated by a protein kinase cascade consisting of a MAPK kinase (MKK) and a MAPK kinase kinase (MAPKKK). beta-Arrestin-2 acts as a scaffold by directly binding to the JNK3 isoform and also by recruiting MKK4 and the MAPKKK apoptosis-signaling kinase-1 (ASK1). In this study, we demonstrate by co-precipitation that the extended N-terminal region of JNK3 mediates binding to the C terminus of beta-arrestin-2 and that the N terminus of JNK3 is required for its activation via beta-arrestin-2. We have used site-specific mutagenesis to identify key residues within the N terminus of JNK3 that are essential for binding and demonstrate that this region represents an independent beta-arrestin-2 binding motif that can be fused to other MAPKs and permit their recruitment to the scaffold complex. In addition, we demonstrate that JNK3 recruits MKK4 to the beta-arrestin-2 scaffold complex by binding to the MAPK docking domain (D-domain) located within the N terminus of MKK4. These findings uncover molecular determinants of beta-arrestin-2 scaffold complex assembly and assign a previously unrecognized role for the unique extended N terminus of JNK3.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available