Functional association between the human myeloid immunoglobulin A Fc receptor (CD89) and FcR gamma chain. Molecular basis for CD89/FcR gamma chain association

• Published in: The Journal of biological chemistry 1995-12, Vol.270 (50), p.29781
• Main Authors: Morton, H C, van den Herik-Oudijk, I E, Vossebeld, P, Snijders, A, Verhoeven, A J, Capel, P J, van de Winkel, J G
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigens, CD - biosynthesis; Antigens, CD - isolation & purification; Antigens, CD - metabolism; Arginine; B-Lymphocytes; Base Sequence; Cell Line; Cell Membrane - immunology; DNA Primers; Gene Expression; Histidine; Humans; Immunoglobulin A - metabolism; Interleukin-2 - biosynthesis; Kinetics; Leukemia, Myeloid; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Point Mutation; Polymerase Chain Reaction; Receptors, Fc - biosynthesis; Receptors, Fc - isolation & purification; Receptors, Fc - metabolism; Receptors, IgG - biosynthesis; Receptors, IgG - isolation & purification; Receptors, IgG - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Transfection; Tumor Cells, Cultured
• ISSN: 0021-9258
• DOI: 10.1074/jbc.270.50.29781

FcR gamma chain has previously been shown to interact with the TCR-CD3 complex, the IgE Fc receptor I (Fc epsilon RI), and the class I and IIIA IgG receptors (Fc gamma RI and Fc gamma RIIIa). Here, we demonstrate that the Fc receptor gamma chain associates with Fc alpha R in transfected IIA1.6 B lymphocytes. Fc alpha R could be expressed at the surface of IIA1.6 B cells by itself, but was devoid of signaling capacity. Upon co-expression of FcR gamma chain, a physical interaction with Fc alpha R could be demonstrated. This association proved crucial for the triggering of both proximal (intracellular calcium increase and tyrosine phosphorylation), as well as distal (IL-2 release), signal transduction responses. We next tested the hypothesis that a positively charged arginine residue (Arg209) within the transmembrane domain of Fc alpha R promotes association with FcR gamma chain. We therefore constructed Fc alpha R molecules where Arg209 was mutated to either a positively charged histidine, a negatively charged aspartic acid, or an uncharged leucine. A functional association between Fc alpha R and FcR gamma chain was observed only with a positively charged residue (Arg209 or His209) present within the Fc alpha R transmembrane domain. These data show that transmembrane signal transduction by the Fc alpha R is mediated via FcR gamma chain, and that Fc alpha R requires a positively charged residue within the transmembrane domain to promote functional association.