The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated protein kinase ERK

J. Paige Adams, Anne E. Anderson, Andrew W. Varga, Kelly T. Dineley, Richard G. Cook, Paul J. Pfaffinger, J. David Sweatt

Research output: Contribution to journalArticlepeer-review

202 Scopus citations


The mitogen-activated protein kinase ERK has recently become a focus of studies of synaptic plasticity and learning and memory. Due to the prominent role of potassium channels in regulating the electrical properties of membranes, modulation of these channels by ERK could play an important role in mediating learning-related synaptic plasticity in the CNS. Kv4.2 is a Shal-type potassium channel that passes an A-type current and is localized to dendrites and cell bodies in the hippocampus. The sequence of Kv4.2 contains several consensus sites for ERK phosphorylation. In the present studies, we tested the hypothesis that Kv4.2 is an ERK substrate. We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr602, Thr607, and Ser616. We used this information to develop antibodies that recognize Kv4.2 phosphorylated by ERK2. One of our phospho-site-selective antibodies was generated using a triply phosphorylated peptide as the antigen. We determined that this antibody recognizes ERK-phosphorylated Kv4.2 in COS-7 cells transfected with Kv4.2 and native ERK-phosphorylated Kv4.2 in the rat hippocampus. These observations indicate that Kv4.2 is a substrate for ERK in vitro and in vivo, and suggest that ERK may regulate potassium-channel function by direct phosphorylation of the pore-forming a subunit.

Original languageEnglish (US)
Pages (from-to)2277-2287
Number of pages11
JournalJournal of neurochemistry
Issue number6
StatePublished - 2000
Externally publishedYes


  • Epilepsy
  • Hippocampus
  • Long-term potentiation
  • Phosphorylation
  • Suprasynaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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