FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation.
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.
Pubmed ID: 11034606 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Antigens, CD95 | Apoptosis | Carrier Proteins | 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 | Organ Specificity | Phosphorylation | Protein-Serine-Threonine Kinases | Recombinant Proteins | Saccharomyces cerevisiae Proteins | Transcription, Genetic | Tumor Cells, Cultured