A Cytoplasmic Inhibitor of the JNK Signal Transduction Pathway

TLDR

The c‑Jun N‑terminal kinase (JNK) is a stress‑activated MAP kinase implicated in regulating cell growth. The cytoplasmic protein JIP‑1 binds JNK, sequesters it in the cytoplasm, suppresses JNK‑dependent gene expression and cellular proliferation—including Bcr‑Abl‑mediated transformation—demonstrating that JIP‑1 is a specific inhibitor of JNK signaling and that protein targeting modulates stress‑activated MAP kinase pathways.

Abstract

The c-Jun amino-terminal kinase (JNK) is a member of the stress-activated group of mitogen-activated protein (MAP) kinases that are implicated in the control of cell growth. A murine cytoplasmic protein that binds specifically to JNK [the JNK interacting protein-1 (JIP-1)] was characterized and cloned. JIP-1 caused cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression. In addition, JIP-1 suppressed the effects of the JNK signaling pathway on cellular proliferation, including transformation by the Bcr-Abl oncogene. This analysis identifies JIP-1 as a specific inhibitor of the JNK signal transduction pathway and establishes protein targeting as a mechanism that regulates signaling by stress-activated MAP kinases.