Activation of extracellular signal-regulated kinase (ERK) and Akt by humanserotonin 5-HT1B receptors in transfected BE(2)-C neuroblastoma cells is inhibited by RGS4

Regulator of G protein signaling (RGS) proteins are GTPase-activating prote ins for hetero trimeric G proteins. One of the best-studied RGS proteins, R GS4, accelerates the rate of GTP hydrolysis by all G(i) and G(q) alpha subu nits yet has been shown to exhibit receptor selectivity. Although RGS4 is e xpressed primarily in brain, its effect on modulating the activity of serot onergic receptors has not yet been reported. In the present study, transfec ted BE(2)-C human neuroblastoma cells expressing human 5-HT1B receptors wer e used to demonstrate that RGS4 can inhibit the coupling of 5-HT1B. recepto rs to cellular signals. Serotonin and sumatriptan were found to stimulate a ctivation of extracellular signal-regulated kinase. This activation was att enuated, but not completely inhibited, by RGS4. Similar inhibition by RGS4 of the protein kinase Akt was also observed. As RGS4 is expressed at high l evels in brain, these results suggest that it may play a role in regulating serotonergic pathways.