TY - JOUR
T1 - Modulation of FcγRI (CD64) ligand binding by blocking peptides of periplakin
AU - Beekman, Jeffrey M.
AU - Bakema, Jantine E.
AU - Van Der Linden, Joke
AU - Tops, Bastiaan
AU - Hinten, Marja
AU - Van Vugt, Martine
AU - Van De Winkel, Jan G.J.
AU - Leusen, Jeanette H.W.
PY - 2004/8/6
Y1 - 2004/8/6
N2 - FcγRI requires both the intracellular domain of the α-chain and associated leukocyte Fc receptor (FcR) γ-chains for its biological function. We recently found the C terminus of periplakin to selectively interact with the cytoplasmic domain of the FcγRI α-chain. It thereby enhances the capacity of FcγRI to bind, internalize, and present antigens on MHC class II. Here, we characterized the domains involved in FcγRI-periplakin interaction using truncated and alanine-substituted FcγRI mutants and randomly mutagenized periplakin. This allowed us to design TAT peptides that selectively interfered with endogenous FcγRI-periplakin interactions. The addition of these peptides to FcγRI-expressing cells modulated FcγRI ligand binding, as assessed by erythrocyte-antibody-rosetting. These data support a dominant-negative role of C-terminal periplakin for FcγRI biological activity and implicate periplakin as a novel regulator of FcγRI in immune cells.
AB - FcγRI requires both the intracellular domain of the α-chain and associated leukocyte Fc receptor (FcR) γ-chains for its biological function. We recently found the C terminus of periplakin to selectively interact with the cytoplasmic domain of the FcγRI α-chain. It thereby enhances the capacity of FcγRI to bind, internalize, and present antigens on MHC class II. Here, we characterized the domains involved in FcγRI-periplakin interaction using truncated and alanine-substituted FcγRI mutants and randomly mutagenized periplakin. This allowed us to design TAT peptides that selectively interfered with endogenous FcγRI-periplakin interactions. The addition of these peptides to FcγRI-expressing cells modulated FcγRI ligand binding, as assessed by erythrocyte-antibody-rosetting. These data support a dominant-negative role of C-terminal periplakin for FcγRI biological activity and implicate periplakin as a novel regulator of FcγRI in immune cells.
KW - Alanine
KW - Amino Acid Sequence
KW - Animals
KW - Binding Sites
KW - Cytoskeletal Proteins/chemistry
KW - Erythrocytes/immunology
KW - Flow Cytometry
KW - Humans
KW - Mice
KW - Molecular Sequence Data
KW - Mutagenesis
KW - Peptide Fragments/chemistry
KW - Plakins
KW - Polymerase Chain Reaction
KW - Receptors, IgG/chemistry
KW - Recombinant Fusion Proteins
KW - Rosette Formation
KW - Saccharomyces cerevisiae/genetics
KW - Structure-Activity Relationship
KW - Transfection
KW - Two-Hybrid System Techniques
UR - http://www.scopus.com/inward/record.url?scp=4043133804&partnerID=8YFLogxK
U2 - 10.1074/jbc.M401018200
DO - 10.1074/jbc.M401018200
M3 - Article
C2 - 15161926
AN - SCOPUS:4043133804
SN - 0021-9258
VL - 279
SP - 33875
EP - 33881
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 32
ER -