Figure 1. The PLCγ₂ S707 point mutants identified in ibrutinib resistance of CLL display enhanced basal activity in cultured mammalian cells.

Left panels, comparison of PLCγ₂S707Y to the PLCγ₂ ibrutinib resistance mutants R665W and L845F. COS-7 cells were transfected as indicated with 500 ng/well of either empty vector (Control) or increasing amounts (15, 50, 150, and 500 ng DNA/well) of vector encoding either wild-type PLCγ₂ (WT), PLCγ₂R665W (R665W), PLCγ₂L845F (L845F), or PLCγ₂S707Y (S707Y). The results shown in the two panels are from separate experiments. Right panel, comparison to the PLCγ₂ ibrutinib resistance mutants S707F and S707P. COS-7 cells were transfected as in the center panel, except that vectors encoding PLCγ₂S707F (S707F) or PLCγ₂S707P (S707P) were used where indicated at the abscissa. Twenty four hours after transfection, the cells were incubated for 18 h with myo-[2-³H]inositol, and inositol phosphate formation was then determined.