PHYSICAL AND FUNCTIONAL ASSOCIATION OF P56LCK WITH FC-GAMMA-RIIIA (CD16) IN NATURAL-KILLER-CELLS

The transmembrane receptor for immunoglobulin G immune complexes on na tural killer (NK) cells and macrophages, FcgammaRIIIA (CD16), mediates cellular activation through a tyrosine kinase-dependent pathway. We s how that FcgammaRIII crosslinking results in activation of the src-rel ated kinase p56lck in NK cells and demonstrate a physical association of p56lck with FcgammaRIIIA in immunoprecipitates from NK cells obtain ed using anti-FcgammaRIII antibodies or immune complexes. Our studies show that the zeta chain, the signal transducing subunit of FcgammaRII IA and of T cell receptor, associates with p56lck and, in NK cells, is a substrate for this kinase. Such direct association of p56lck with t he zeta subunit was confirmed by demonstrating the interaction in hete rologous cells transfected with cDNA expressing p56lck and zeta. Our f indings demonstrate both functional and physical association of p56lck with FcgammaRIIIA, through direct interaction of the kinase with the zeta and/or the gamma signal transducer subunits of the receptor. Thes e data suggest a possible mechanism by which activation via FcgammaRII IA occurs.