J. Yanagisawa et al., THE MOLECULAR INTERACTION OF FAS AND FAP-1 - A TRIPEPTIDE BLOCKER OF HUMAN FAS INTERACTION WITH FAP-1 PROMOTES FAS-INDUCED APOPTOSIS, The Journal of biological chemistry, 272(13), 1997, pp. 8539-8545
Fas (APO-1/CD95), which isa member of the tumor necrosis factor recept
or superfamily, is a cell surface receptor that induces apoptosis. A p
rotein tyrosine phosphatase, Fas-associated phosphatase-l (FAP-1), tha
t was previously identified as a Fas binding protein interacts with th
e C-terminal 15 amino acids of the regulatory domain of the Fas recept
or. 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 n
ecessary 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 ap
optosis 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 recepto
rs have been shown to interact with PDZ domain in signal transducing m
olecules, this may represent a general motif for protein-protein inter
actions with important biological functions.