FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation

J Exp Med. 2000 Oct 16;192(8):1165-74. doi: 10.1084/jem.192.8.1165.

Abstract

Fas is a cell surface death receptor that signals apoptosis. Several proteins have been identified that bind to the cytoplasmic death domain of Fas. Fas-associated death domain (FADD), which couples Fas to procaspase-8, and Daxx, which couples Fas to the Jun NH(2)-terminal kinase pathway, bind independently to the Fas death domain. We have identified a 130-kD kinase designated Fas-interacting serine/threonine kinase/homeodomain-interacting protein kinase (FIST/HIPK3) as a novel Fas-interacting protein. Binding to Fas is mediated by a conserved sequence in the COOH terminus of the protein. FIST/HIPK3 is widely expressed in mammalian tissues and is localized both in the nucleus and in the cytoplasm. In transfected cell lines, FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction. Although Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3, cell death is not affected. These results suggest that Fas-associated FIST/HIPK3 modulates one of the two major signaling pathways of Fas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • Fas-Associated Death Domain Protein
  • Female
  • Gene Library
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Organ Specificity
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • fas Receptor / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • FADD protein, human
  • Fadd protein, mouse
  • Fas-Associated Death Domain Protein
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • fas Receptor
  • Protein-Serine-Threonine Kinases
  • YAK1 protein, S cerevisiae
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases