A cytoplasmic inhibitor of the JNK signal transduction pathway

Science. 1997 Aug 1;277(5326):693-6. doi: 10.1126/science.277.5326.693.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activating Transcription Factor 2
  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Cloning, Molecular
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cytoplasm / metabolism
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression Regulation
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection

Substances

  • Activating Transcription Factor 2
  • Carrier Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-jun
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Fusion Proteins, bcr-abl
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases

Associated data

  • GENBANK/AF003115