The JNK group of MAPKs is activated by a variety of inflammatory cytokines and environmental stressors. Activated JNK phosphorylates many cellular proteins, such as components of the AP-1 transcription factor complex (c-Jun and ATF-2). JNK-interacting proteins (JIPs) bind JNK, MKK7, MLKs, p190RhoGEF, and the Ste20-related protein kinase HPK1. In mouse, alternative splicing of JIP produces multiple splice variants, JIP-1, JIP-1b, JIP-2a, JIP-2b, and JIP-3. The structure of full length JIP consists of two N-terminal acidic regions, a JNK binding domain (JBD), two proline rich regions (PR), and both an SH3 and a phosphotyrosine-binding domain in the C-terminal region. JIP-1 localizes to the tips of neurites in differentiated PC12 cells, and may interact with JNK, MKK7, and MLK to facilitate formation of the JNK activating complex. IB1 is the rat homologue of JIP-1b, a JIP-1 variant that includes a 47 amino acid insert in the C-terminal region. IB1 is found in the nucleus and cytoplasm, and may function as a transactivator of the GLUT2 gene. Thus, JIP-1 and its related isoforms may have multiple functions that involve specific protein-protein interactions.
Synonyms: JNK Interacting Protein