Hck/Lyn doubly deficient mast cells exhibit an intermediate activation phenotype between Hck- or Lyn-deficient cells, and positive and negative regulation via FcϵRI β subunit is exerted by Lyn-mediated phosphorylation of the canonical and noncanonical tyrosine residues. IgE-sensitized mast cells of the indicated genotypes and FcϵRIβ-transduced cells were stimulated with 1 (□), 10 (░), or 100 (■) ng/mL DNP₂₃-HSA for 45 minutes (A) or 20 hours (B). Histamine and IL-6 secreted into culture media were measured. ND indicates not detected. Representative results from 2 independent transduction experiments are shown. Error bars represent SD.