Functional association between the human myeloid immunoglobulin A Fc receptor (CD89) and FcR gamma chain. Molecular basis for CD89/FcR gamma chain association.
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.
Department of Immunology, University Hospital Utrecht, The Netherlands.
H C
HC
Morton
I E
IE
van den Herik-Oudijk
P
P
Vossebeld
A
A
Snijders
A J
AJ
Verhoeven
P J
PJ
Capel
J G
JG
van de Winkel
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D001120:Arginine; D001402:B-Lymphocytes; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D017931:DNA Primers; D015870:Gene Expression; D006639:Histidine; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D007951:Leukemia, Myeloid; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011961:Receptors, Fc / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D017931:DNA Primers; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007376:Interleukin-2; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D006639:Histidine; D001120:Arginine