The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis.

Abstract

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.

• Authors: J Yanagisawa, M Takahashi, H Kanki, H Yano-Yanagisawa, T Tazunoki, E Sawa, T Nishitoba, M Kamishohara, E Kobayashi, S Kataoka, T Sato
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 272 Issue 13 Pg. 8539-45 (Mar 28 1997) ISSN: 0021-9258 [Print] United States
• PMID: 9079683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• Carrier Proteins
• FAF1 protein, human
• FBF1 protein, human
• Faf1 protein, mouse
• Intracellular Signaling Peptides and Proteins
• Oligopeptides
• Potassium Channels
• Receptors, N-Methyl-D-Aspartate
• Transcription Factors
• acetyl-seryl-leucyl-valine
• Protein Phosphatase 1
• PTPN13 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 13
• Protein Tyrosine Phosphatases
• Ptpn13 protein, mouse
• Ptpn13 protein, rat

Topics

• Adaptor Proteins, Signal Transducing
• Alternative Splicing
• Amino Acid Sequence
• Animals
• Apoptosis
• Apoptosis Regulatory Proteins
• Carrier Proteins (metabolism)
• Helix-Loop-Helix Motifs
• Humans
• Intracellular Signaling Peptides and Proteins
• Mice
• Microinjections
• Molecular Sequence Data
• Oligopeptides (pharmacology)
• Peptide Mapping
• Potassium Channels (metabolism)
• Protein Phosphatase 1
• Protein Tyrosine Phosphatase, Non-Receptor Type 13 (metabolism)
• Protein Tyrosine Phosphatases (metabolism)
• Rats
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Transcription Factors (metabolism)
• Tumor Cells, Cultured