NCAM stimulates the Ras-MAPK pathway and CREB phosphorylation in neuronal cells

Ralf Steffen Schmid, Ronald D. Graft, Michael D. Schaller, Suzhen Chen, Melitta Camartin, John J. Hemperly, Patricia F. Maness

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182 Scopus citations


The neural cell adhesion molecule NCAM plays an important role in axonal growth, learning, and memory. A signaling pathway has been elucidated in which clustering of the NCAM140 isoform in the neural plasma membrane stimulated the activating phosphorylation of mitogen-activated protein kinases (MAPKs) and the transcription factor cyclic AMP response-element binding protein (CREB). NCAM clustering transiently induced dual phosphorylation (activation) of the MAPKs ERK1 and ERK2 (extracellular signal-regulated kinases) by a pathway regulated by the focal adhesion kinase p125(fak), p59(fyn), Ras, and MAPK kinase. CREB phosphorylation at serine 133 induced by NCAM was dependent in part on an intact MAPK pathway. c-Jun N- terminal kinase, which is associated with apoptosis and cellular stress, was not activated by NCAM. Inhibition of the MAPK pathway in rat cerebellar neuron cultures selectively reduced NCAM-stimulated neurite outgrowth. These results define an NCAM signal transduction mechanism with the potential for modulating the expression of genes needed for axonal growth, survival, and synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)542-558
Number of pages17
JournalJournal of Neurobiology
Issue number4
StatePublished - 1999

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience


  • CREB
  • MAP kinase
  • Neural cell adhesion molecules
  • Neurite outgrowth
  • Synaptic plasticity

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