(A to E) COS7 cells were transfected with CKAR2 alone (endogenous; gray) or co-transfected with CKAR2 and the indicated mCherry-tagged PKCγ construct: WT PKCγ (orange), a PKCγ lacking a pseudosubstrate (ΔPS), or the indicated pseudosubstrate SCA14 mutants in (A); the ΔC1A or ΔF48 (C1A domain) in (B); the ΔC1B or C1B SCA14 mutants in (C); the ΔC2 or C2 SCA14 mutants in (D); or the kinase-domain and C-tail SCA14 mutants in (E). PKC activity was monitored by measuring FRET/CFP ratio changes after sequential addition of 100 μM UTP, 200 nM PDBu, and 50 nM Calyculin A at the indicated times. Data were normalized to the endpoint (1.0) and show mean ± S.E.M. from at least two independent experiments, N ≥ 17 (A), ≥ 16 (B), ≥ 19 (C), ≥ 11 (D), and ≥ 33 (E) cells per condition. In (B) through (E), the PKCγ WT and endogenous data (dashed lines) are reproduced from (A) for comparison. (F) Quantification of percent increase in basal activity in (A to E) over WT PKCγ.