ERKI/II regulation by the muscarinic acetylcholine receptors in neurons

Kobi Rosenblum, Marie Futter, Matthew Jones, E. C. Hulme, T. V.P. Bliss

Research output: Contribution to journalArticlepeer-review


Muscarinic acetylcholine receptors (mAChRs) are known to be involved in learning and memory, but the molecular basis of their involvement is not well understood. The availability of new and specific biochemical tools has revealed a crucial role for the mitogen-activated protein kinase (MAPK) family in learning and memory. Here, we examine the link between mAChRs and MAPK in neurons. Using the MAPK kinase (MEK)-specific inhibitor PD98059, we first demonstrate a necessary role for active ERKI/II in long-term potentiation in vivo. Using phospho-specific antibodies that recognize the activated form of ERKI/II, we find that the level of ERKI/II activation in brain is regulated by mAChRs. Carbachol, a muscarinic agonist, induces prolonged activation of ERKI/II, without effect on the related kinase SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal protein kinase) in primary cortical cultures. ERKI/II activation is Src-dependent and partially phosphoinositide-3 kinase- and Ca2+-dependent but is PKC-independent. M1-M4 mAChR subtypes expressed in COS-7 cells can all induce ERKI/II activation using a signal transduction pathway similar to that operating in neurons. The nature of the signal transduction suggests that ERKI/II can serve as a convergence site for mAChR activation and other neurotransmitter receptors.

Original languageEnglish
Pages (from-to)977-985
Number of pages9
JournalJournal of Neuroscience
Issue number3
StatePublished - 1 Feb 2000
Externally publishedYes


  • COS-7
  • Extracellular regulated kinase
  • LTP
  • MAPK
  • Neurons
  • Signal transduction
  • mAChR

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'ERKI/II regulation by the muscarinic acetylcholine receptors in neurons'. Together they form a unique fingerprint.

Cite this