Fig. 3: P38 phosphorylates Kv4.2 at a C-terminal Pin1 binding site.
From: Activity-dependent isomerization of Kv4.2 by Pin1 regulates cognitive flexibility
a P38 phosphorylates Kv4.2 at Thr602 and Thr607. Kv4.2 and p38α constructs (agf: p38 kinase dead mutant) were co-transfected into HEK-293T cells. Lysates were analyzed by western blotting with anti-pT602 and anti-pT607 specific antibodies. n = 15 for ctl, 9 for p38 and p38 agf. T-test, ***p < 0.001. b p38 binds to Kv4.2. Kv4.2 and p38α were co-transfected into HEK-293T cells. Detergent lysates were incubated with anti-Myc antibody and analyzed by western blotting with anti-Flag and anti-Myc antibodies. Data was repeated in two independent experiments. c, Enriched novel environment activates p38 in mouse hippocampus. n = 6 in each group. T-test, *p < 0.05. d KA-induced seizure activates p38 in mouse hippocampus. n = 8 in each group. T-test, ***p < 0.001. e PTZ-induced seizure activates p38 in mouse hippocampus. n = 6 for ctl and 5 for PTZ. T-test, ***p < 0.001. f SB203580, a potent p38 inhibitor (20 mg/kg, i.p., 15 min) blocked PTZ-induced phosphorylation of Kv4.2 T607 in mouse hippocampus. n = 4 in each group. T-test, **p < 0.01. g SL327, a selective MEK inhibitor (30 mg/kg, i.p., 15 min) did not block PTZ-induced phosphorylation of Kv4.2 T607 in mouse hippocampus. n = 7 in each group. *p < 0.05, **p < 0.01. t-test. Data are presented as mean ± SEM.
