PHYSICAL AND FUNCTIONAL ASSOCIATION OF THE HIGH-AFFINITY IMMUNOGLOBULIN-G RECEPTOR (FC-GAMMA-RI) WITH THE KINASES HCK AND LYN

The high affinity immunoglobulin G (IgG) receptor Fc gamma RI (CD64) i s expressed constitutively on monocytes and macrophages, and is induci ble on neutrophils. Fc gamma RI has recently been shown to be associat ed with the signal transducing gamma subunit of the high-affinity IgE receptor (Fc epsilon RI gamma). Induction of cytoplasmic protein tyros ine phosphorylation by Fc gamma RI cross-linking is known to be import ant in mediating Fc gamma RI-coupled effector functions. Recently, syk has been implicated in this role. We now report that the src-type kin ases hck and lyn are physically and functionally associated with Fc ga mma RI. Hck and lyn coimmunoprecipitated with Fc gamma RI from deterge nt lysates of normal human monocytes and of the monocytic line THP-1. Hck and lyn showed rapidly increased phosphorylation and increased exo genous substrate kinase activity after cross-linking of Fc gamma RI. T hese results demonstrate both physical and functional association of t he Fc gamma RI/Fc epsilon RI gamma receptor complex with hck and lyn, and suggest a potential signal transducing role for these kinases in m onocyte/macrophage activation.