Serotonin activation of the ERK pathway in Hermissenda: contribution of calcium-dependent protein kinase C

The mitogen-activated protein kinase (MAPK) cascade is an important contrib utor to synaptic plasticity and learning in both vertebrates and invertebra tes. In the nudibranch mollusk Hermissenda, phosphorylation and activation of the extracellular signal-regulated protein kinase (ERK), a key member of a MAPK cascade, is produced by one-trial and multitrial Pavlovian conditio ning. Several signal transduction pathways that are activated by 5-hydroxyt ryptamine (5-HT) and may contribute to conditioning have been identified in type B photoreceptors. However, the regulation of ERK activity by 'upstrea m' signaling molecules has not been previously investigated in Hermissenda. In the present study we examined the role of protein kinase C (PKC) in the serotonin (5-HT) activation of the ERK pathway. The phorbol ester TPA prod uced an increase in ERK phosphorylation that was blocked by the PKC inhibit ors GF109203X or Go6976. TPA-dependent ERK phosphorylation was also blocked by the MEK1 inhibitors PD098059 or U0126, The increased phosphorylation of ERK by 5-HT was reduced but not blocked by pretreatment with the calcium c helator BAPTA-AM or pretreatment with Go6976 or GF109203X. These results in dicate that Ca2+-dependent PKC activation contributes to ERK phosphorylatio n, although a PKC-independent pathway is also involved in 5-HT-dependent ER K phosphorylation and activation.