PKA-mediated activation of ERK1/2 underlies adenosine-ADORA2B-mediated erythrocyte SphK1 activation in WT mice and normal human individuals. SphK1 activity, membrane bound total, and phosphorylated SphK1 in primary erythrocytes from WT mice (A and C) and normal human subjects (B and D) after treatment with N (10 μM NECA), N+M (10 μM NECA + 10 μM MRS1754), N+H (10 μM NECA + 10 μM H89), N+P (10 μM NECA + 20 μM PD98059), F (10 μM Forskolin), and F+P (10 μM Forskolin+ 20 μM PD98059) for 30 minutes. Values shown represent the mean ± SEM (n = 5 for normal human subjects and n = 4 for WT mice). *P < .05 N or F vs control; **P < .05 N+M, N+H, N+P vs N; ***P < .05 F+P vs F.