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 contributor to synaptic plasticity and learning in both vertebrates and invertebrates. 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 conditioning. Several signal transduction pathways that are activated by 5-hydroxytryptamine (5-HT) and may contribute to conditioning have been identified in type B photoreceptors. However, the regulation of ERK activity by 'upstream' 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 produced an increase in ERK phosphorylation that was blocked by the PKC inhibitors GF109203X or Gö6976. 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 chelator BAPTA-AM or pretreatment with Gö6976 or GF109203X. These results indicate that Ca(2+)-dependent PKC activation contributes to ERK phosphorylation, although a PKC-independent pathway is also involved in 5-HT-dependent ERK phosphorylation and activation.
Crow
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T
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Texas, USA. terry.crow@uth.tmc.edu
Xue-Bian
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Siddiqi
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Neary
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008974:Mollusca / Q000502:physiology*; D010766:Phosphorylation; D012701:Serotonin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002227:Carbazoles; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C081021:Go 6976; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D012701:Serotonin; D004533:Egtazic Acid; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium