METHOD FOR SPECIFIC REGULATION OF TOLL-LIKE RECEPTOR/INTERLEUKIN-18 SIGNALING BY MUTATION-INTRODUCED MYD88 PROTEIN

摘要

Disclosed is a technique for regulating the function of a cytoplasmic factor, an adapter molecule MyD88, in a cell in a signal-specific manner, wherein the adapter molecule MyD88 is used for a signaling common to the TLR family members (e.g., LPS) and the IL-1 receptor family members. Specifically disclosed is a MyD88 TIR mutant protein selected from the following proteins (a), (b) and (c) or a salt thereof: (a) a protein comprising an amino acid sequence having the substitution of at least one amino acid residue selected from the group consisting of a lysine residue at position-214, a lysine residue at position-238 and an arginine residue at position-269 by other amino acid residue in the amino acid sequence depicted in SEQ ID NO:2; (b) a protein which comprises an amino acid sequence having the deletion, substitution or addition of one or several amino acid residues excluding a lysine residue at position-214, an amino acid residue at position-238 and an amino acid residue at position-269 in the amino acid sequence for the protein (a), and which can inhibit a signaling induced by the stimulation by a lipopolysaccharide but cannot inhibit a signaling induced by the stimulation by interleukin-18; and (c) a protein which is encoded by DNA capable of hybridizing with DNA complementary to DNA comprising the nucleotide sequence depicted in SEQ ID NO:3, 5 or 7 under stringent conditions, and which can inhibit a signaling induced by the stimulation by a lipopolysaccharide but cannot inhibit a signaling induced by the stimulation by interleukin-18.