TY - JOUR
T1 - Cytoplasmic Tails of Human Complement Receptor Type 3 (CR3, CD11b/CD18) Regulate Ligand Avidity and the Internalization of Occupied Receptors
AU - Rabb, Hamid
AU - Michishita, Masahiro
AU - Sharma, Chander P.
AU - Brown, Dennis
AU - Arnaout, M. Amin
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1993/7/15
Y1 - 1993/7/15
N2 - To evaluate the role of the cytoplasmic tails of CD11b and CD18 in ligand binding and internalization of the human complement receptor type 3 (CR3, CD11b/CD18), wild type, and truncation mutants of CD11b and CD18 cDNA were expressed in COS fibroblastoid cells and assayed for surface membrane expression, ligand binding, and internalization. Truncated CD11b (α1119T) and CD18 (β728T) subunits retaining, respectively, two and five residues of the putative cytoplasmic tails were generated by in vitro mutagenesis. Binding of α1119Tβ and αβ728T heterodimeric receptors to iC3b was increased by 330% and 210%, respectively, relative to wild type CR3, suggesting that both cytoplasmic tails of CR3 negatively control receptor avidity. Internalization of antibody cross-linked wild type CR3 occurred predominantly through coated pits. Truncation of the cytoplasmic tail of CD18 but not of CD11b markedly reduced coated pit internalization of CR3, an effect also produced by a single F754A mutation involving one of two putative NPXF internalization signals in CD18.
AB - To evaluate the role of the cytoplasmic tails of CD11b and CD18 in ligand binding and internalization of the human complement receptor type 3 (CR3, CD11b/CD18), wild type, and truncation mutants of CD11b and CD18 cDNA were expressed in COS fibroblastoid cells and assayed for surface membrane expression, ligand binding, and internalization. Truncated CD11b (α1119T) and CD18 (β728T) subunits retaining, respectively, two and five residues of the putative cytoplasmic tails were generated by in vitro mutagenesis. Binding of α1119Tβ and αβ728T heterodimeric receptors to iC3b was increased by 330% and 210%, respectively, relative to wild type CR3, suggesting that both cytoplasmic tails of CR3 negatively control receptor avidity. Internalization of antibody cross-linked wild type CR3 occurred predominantly through coated pits. Truncation of the cytoplasmic tail of CD18 but not of CD11b markedly reduced coated pit internalization of CR3, an effect also produced by a single F754A mutation involving one of two putative NPXF internalization signals in CD18.
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M3 - Article
C2 - 8101539
AN - SCOPUS:0027272743
SN - 0022-1767
VL - 151
SP - 990
EP - 1002
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -