Ser-890 in the C1 cassette reduces PKC potentiation. (A) Amino acid sequence of the C1 cassette of the NR1 subunit. Serine residues 889, 890, 896, and 897 were mutated to alanines, singly or in combination. (B) Currents recorded in Ca2+ Ringer's solution from oocytes expressing NR1111/NR2A, NR1111(S889–897A)/NR2A, and NR1101/NR2A receptors before (Upper) and after (Lower) incubation with TPA. Potentiation of NR1111(S889–897A)/NR2A receptors was greater than that for NR1111/NR2A receptors. (C) Mean PKC potentiation of wild-type (WT) and mutant receptors in Ca2+ Ringer's solution. TPA potentiation of wild-type NR1111, NR1111(S889A), NR1111(S890A), NR1111(S896A), NR1111(S897A), NR1111(S889–897A)/NR2A, and wild-type NR1101/NR2A was to 5.7 ± 0.5 (n = 7), 5.2 ± 0.5 (n = 3), 7.9 ± 0.4 (n = 6; *, P < 0.05 vs. NR1111/NR2A), 4.7 ± 0.3 (n = 3), 5.0 ± 0.5 (n = 3), 8.2 ± 0.8 (n = 7; *, P < 0.05 vs. NR1111/NR2A), and 10.0 ± 0.8 [n = 6; ***, P < 0.001 vs. NR1111; **, P < 0.01 vs. NR1111(S890A) and NR1111(S889–897A)] times control, respectively.