The cytoplasmic domain of human Fc gamma RIa alters the functional properties of the Fc gamma RI center dot gamma-chain receptor complex

The gamma/zeta-chain family of proteins mediate cell activation for multipl e immunoglobulin receptors, However, the recognition that these receptors m ay have distinct biologic functions suggests that additional signaling elem ents may contribute to functional diversity. We hypothesized that the cytop lasmic domain (CY) of the ligand binding alpha-chain alters the biological properties of the receptor complex. Using macrophage Fc gamma RIa as a mode l system, we created stable transfectants expressing a full-length or a CY deletion mutant of human Fc gamma RIa. Both receptors functionally associat e with the endogenous murine gamma-chain. However, we have established that the CY of Fc gamma RIa directly contributes to the functional properties o f the receptor complex. Deletion of the Fc gamma RIa CY leads to slower kin etics of receptor-specific phagocytosis and endocytosis as well as lower to tal phagocytosis despite identical levels of receptor expression. Deletion of the CY also converts the phenotype of calcium independent Fc gamma RIa-s pecific phagocytosis to a calcium-dependent phenotype, Finally, deletion of the CY abrogates Fc gamma RIa-specific secretion of interleukin-6 but does not, affect production of interleukin-1 beta These results demonstrate a f unctional role for the CY of Fc gamma RIa and provide a general model for u nderstanding how multiple receptors that utilize the gamma-chain can genera te diversity in function.