Aggregation of the high-affinity receptor for IgE (FcεRI) on the surface of intact or permeabilized rodent mast cells results in tyrosine phosphorylation of phospholipase C-γl (PLCγ2) and PLCγ2, and translocation of both isozymes to the particulate fraction. We report here that activation of resident tirosine kinases by the addition of adenosine triphosphate (ATP), orthovanadate, and Mg2+ to rat basophilic leukemia cell (RBL) lysates induces an association of PLCγ2 with the Triton-insoluble particulate fraction, with a parallel increase in tyrosine phosphorylation of cellular proteins. Both PLCγ2 translocation and tyrosine phosphorylation are supported by millimolar Mg2+ or Mn2+ but not by Ca2+. Both tyrosine phosphorylation and PLCγ2 translocation are inhibited by genistein. These data suggest that in vitro activation of tyrosine kinase activity in broken cell preparations induces the formation of associations between PLCγ2 and ligands within the Triton-insoluble fraction.