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 I IIA IgG receptors (Fc gamma RI and Fc gamma RIIIa). Here, we demonstra te that the Fc receptor gamma chain associates with Fc alpha R in tran sfected IIA1.6 B lymphocytes. Fc alpha R could be expressed at the sur face of IIA1.6 B cells by itself, but was devoid of signaling capacity . Upon co-expression of FcR gamma chain, a physical interaction with F c alpha R could be demonstrated. This association proved crucial for t he triggering of both proximal (intracellular calcium increase and tyr osine phosphorylation), as well as distal (IL-2 release), signal trans duction responses. We next tested the hypothesis that a positively cha rged arginine residue (Arg(209)) within the transmembrane domain of Fc alpha R promotes association with FcR gamma chain. We therefore const ructed Fc alpha R molecules where Arg(209) was mutated to either a pos itively charged histidine, a negatively charged aspartic acid, or an u ncharged leucine. A functional association between Fc alpha R and FcR gamma chain was observed only with a positively charged residue (Arg(2 09) or His(209)) present within the Fc alpha R transmembrane domain. T hese data show that transmembrane signal transduction by the Fc alpha R is mediated via FcR gamma chain, and that Fc alpha R requires a posi tively charged residue within the transmembrane domain to promote func tional association.