Requirement of EGF receptor kinase for signaling by calcium-induced ERK activation and neurite outgrowth in PC12 cells

Jung Gyu Park, Youngah Jo, Yun Taik Kim, Young Sook Yoo

Research output: Contribution to journalArticlepeer-review


Membrane depolarization in PC12 cells induces calcium influx via an L-type voltage-sensitive calcium channel (L-VSCC) and increases intracellular free calcium, which leads to tyrosine phosphorylation of epidermal growth factor (EGF) receptor and the associated adaptor protein, Shc. This activated EGF receptor complex then can activate mitogen-activated protein (MAP) kinase, as in nerve growth factor (NGF) receptor activation. In the present study, we investigated the role of EGF receptor in the signaling pathway initiated by membrane depolarization of PC12 cells. Prolonged membrane depolarization induced phosphorylation of extracellular signal-regulated kinase (ERK) within 1 min in undifferentiated PC12 cells. Pretreatment of PC12 cells with the calcium chelator EGTA abolished depolarization-stimulated ERK phosphorylation, but NGF-induced phosphorylation of ERK was not affected. The chronic treatment of phorbol ester, which down-regulated the activity of protein kinase C (PKC), did not affect the phosphorylation of ERK upon depolarization. In the presence of an inhibitor of EGF receptor, neither depolarization nor calcium ionophore increased the level of ERK phosphorylation. These data imply that the EGF receptor is functionally necessary to activate ERK and neurite outgrowth in response to the prolonged depolarization in PC12 cells, and also that PKC is apparently not involved in this signaling pathway.

Original languageEnglish (US)
Pages (from-to)468-474
Number of pages7
JournalJournal of Biochemistry and Molecular Biology
Issue number5
StatePublished - Sep 30 1998


  • Depolarization
  • Extracellular signal-regulated kinase
  • Neurite outgrowth
  • PC12 cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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