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

V Rochat-Steiner; K Becker; O Micheau; P Schneider; K Burns; J Tschopp

doi:10.1084/jem.192.8.1165

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.

Authors

V Rochat-Steiner¹, K Becker, O Micheau, P Schneider, K Burns, J Tschopp

Affiliation

¹ Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH-1066 Epalinges, Switzerland.

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