Table 1.

Activation of PLCγ₂ by catalytically-inert BTK is not limited to PLCγ₂S707Y but is also observed for other PLCγ₂ variants mediating ibrutinib resistance in CLL cells

COS-7 cells were transfected as indicated with 150 ng/well vector encoding WT PLCγ₂ (PLCγ₂WT); 50 ng/well vector encoding the PLCγ₂ variants D334H, R665W, S707Y, S707F, L845F, D993H, and M1141R; 15 ng of vector encoding PLCγ₂S707P; and 100 ng/well of vector encoding BTKWT or BTK variants K430R, E41K, or E41K/K430R. The ratios of the PLC activities determined in the presence of BTKE41K/K430R and BTKE41K are specified in the right column. The data depicted in the table show representative results from three independent experiments each as mean values of three technical replicates.

BTK	Inositol phosphate formation					Ratio (E41K/K430R:E41K)
	Control	WT	K430R	E41K	E41K/K430R
	cpm					%
PLCγ2WT	67	86	67	2358	121	5.2
PLCγ2D334H	40	1097	236	10089	4390	43.5
PLCγ2R665W	42	374	138	4420	1956	44.3
PLCγ2S707Y	231	1998	713	17442	8132	46.6
PLCγ2S707F	464	2561	1488	20150	11215	55.7
PLCγ2S707P	728	2991	2563	17734	11584	65.3
PLCγ2L845F	219	1660	455	8937	9668	108.2
PLCγ2D993H	702	3604	1888	10808	7892	73.0
PLCγ2M1141R	1966	5858	5395	14268	14187	99.4