| First Author | Wang T | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 24 | Pages | 20999-1003 |
| PubMed ID | 11279197 | Mgi Jnum | J:172900 |
| Mgi Id | MGI:5009191 | Doi | 10.1074/jbc.M101355200 |
| Citation | Wang T, et al. (2001) Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus. J Biol Chem 276(24):20999-1003 |
| abstractText | c-Jun N-terminal kinase (JNK)-mediated cell signaling pathways are regulated endogenously in part by protein-protein interactions with glutathione S-transferase P1-1 (GSTP1-1) (). Using purified recombinant proteins, combined with fluorescence resonance energy transfer technology, we have found that the C terminus of JNK is critical to the interaction with GSTP1-1. The apparent K(d) for full-length JNK was 188 nm and for a C-terminal fragment (residues 200-424) 217 nm. An N-terminal fragment (residues 1-206) did not bind to GSTP1-1. Increased expression of the C-terminal JNK fragment in a tetracycline-inducible transfected NIH3T3 cell line produced a concentration-dependent increase in the kinase activity of JNK under normal, unstressed growth conditions indicating a dominant-negative effect. This suggests that the fragment can compete with endogenous full-length functional JNK resulting in dissociation of the GSTP1-1-JNK interaction and concomitant JNK enzyme activation. By using an antibody to hemagglutinin-tagged C-JNK, a concentration-dependent co-immunoprecipitation of GSTP1-1 was achieved. These data provide evidence for direct interactions between the C-terminal of JNK and GSTP1-1 and a rationale for considering GSTP1-1 as a critical ligand-binding protein with a role in regulating kinase pathways. |
