TY - JOUR
T1 - The molecular interaction of Fas and FAP-1
T2 - A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis
AU - Yanagisawa, Junn
AU - Takahashi, Motoo
AU - Kanki, Hiroaki
AU - Yano-Yanagisawa, Hiroko
AU - Tazunoki, Tetsushi
AU - Sawa, Eiji
AU - Nishitoba, Tsuyoshi
AU - Kamishohara, Masaru
AU - Kobayashi, Eiichi
AU - Kataoka, Shiro
AU - Sato, Takaaki
PY - 1997/3/28
Y1 - 1997/3/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030888599&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.13.8539
DO - 10.1074/jbc.272.13.8539
M3 - Article
C2 - 9079683
AN - SCOPUS:0030888599
SN - 0021-9258
VL - 272
SP - 8539
EP - 8545
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -