Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/13428
Title: Extracellular mutations of non-obese diabetic mouse FcgammaRI modify surface expression and ligand binding.
Authors: Gavin, A L;Hamilton, J A;Hogarth, P Mark
Affiliation: Austin Research Institute, Austin Hospital, Heidelberg, Victoria 3084, Australia.
Issue Date: 19-Jul-1996
Citation: The Journal of Biological Chemistry; 271(29): 17091-9
Abstract: The non-obese diabetic mouse (NOD) expresses a unique form of the high affinity receptor for IgG (FcgammaRI), containing multiple mutations that result in substitutions and insertions of amino acids and a truncated cytoplasmic tail. As a result of these major changes, receptor affinity for IgG increases 10-fold over that of wild-type FcgammaRI from BALB/c mice, while the specificity for ligand is retained. Kinetic analysis revealed that while the association rate of IgG with FcgammaRI from NOD mice (FcgammaRI-NOD) and FcgammaRI from BALB/c mice (FcgammaRI-BALB) is similar, IgG bound much more tightly to FcgammaRI-NOD as revealed by a profoundly diminished dissociation rate. Transfection studies demonstrated that FcgammaRI-NOD was expressed at one-tenth of the level of FcgammaRI-BALB. Although mouse FcgammaRI was previously not known to associate with the FcepsilonRI gamma-subunit, transfection of COS-7 cells demonstrates that like human FcgammaRI, mouse FcgammaRI is also able to associate with this signaling subunit. Furthermore, expression levels of FcgammaRI-NOD were not restored by the presence of the FcepsilonRI gamma-subunit. The difference in the levels of expression was mapped to mutations in the extracellular region of FcgammaRI-NOD as replacement of the extracellular domains with those of human FcgammaRI or FcgammaRI-BALB restored expression to that of human FcgammaRI or FcgammaRI-BALB.
Internal ID Number: 8663283
URI: http://ahro.austin.org.au/austinjspui/handle/1/13428
URL: http://www.ncbi.nlm.nih.gov/pubmed/8663283
Type: Journal Article
Subjects: Amino Acid Sequence
Animals
Bone Marrow.immunology
Bone Marrow Cells
Cell Line
Cercopithecus aethiops
DNA Primers
DNA, Complementary
Diabetes Mellitus, Type 1.genetics.immunology
Flow Cytometry
Humans
Immunoglobulin G.metabolism
Kinetics
Ligands
Macrophages.immunology
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Molecular Sequence Data
Mutagenesis, Site-Directed
Polymerase Chain Reaction
Receptors, IgG.biosynthesis.genetics.metabolism
Recombinant Fusion Proteins.biosynthesis.metabolism
Sequence Homology, Amino Acid
Spleen.immunology
Substrate Specificity
Transfection
Appears in Collections:Journal articles

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