Identification of an Activator of the Microtubule‐Associated Protein 2 Kinases ERK1 and ERK2 in PC12 Cells Stimulated with Nerve Growth Factor or Bradykinin

Natalie G. Ahn, David J. Robbins, John W. Haycock, Rony Seger, Melanie H. Cobb, Edwin G. Krebs

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Treatment of PC 12 pheochromocytoma cells with nerve growth factor (NGF) or bradykinin leads to the activation of extracellular signal-regulated kinases ERK1 and ERK2, two isozymes of microtubule-associated protein 2 (MAP) kinase that are present in numerous cell lines and regulated by diverse extracellular signals. The activation of MAP kinase is associated with its phosphorylation on tyrosine and threonine residues, both of which are required for activity. In the present studies, we have identified a factor in extracts of PC12 cells treated with NGF or bradykinin, named MAP kinase activator, that, when reconstituted with inactive MAP kinase from untreated cells, dramatically increased MAP kinase activity. Activation of MAP kinase in vitro by this factor required MgATP and was associated with the phosphorylation of a 42- (ERK1) and 44-kDa (ERK2) polypeptide. Incorporation of 32P into ERK1 and ERK2 occurred primarily on tyrosine and threonine residues and was associated with a single tryptic peptide, which is identical to one whose phosphorylation is increased by treatment of intact PC12 cells with NGF. Thus, the MAP kinase activator identified in PC12 cells is likely to be a physiologically important intermediate in the signaling pathways activated by NGF and bradykinin. Moreover, stimulation of the activator by NGF and bradykinin suggests that tyrosine kinase receptors and guanine nucleotide-binding protein-coupled receptors are both capable of regulating these pathways.

Original languageEnglish (US)
Pages (from-to)147-156
Number of pages10
JournalJournal of neurochemistry
Volume59
Issue number1
DOIs
StatePublished - Jul 1992
Externally publishedYes

Keywords

  • Bradykinin
  • Microtubule-associated protein 2 kinase
  • Microtubule-associated protein 2 kinase activator
  • Nerve growth factor
  • PC 12 cells
  • Signal transduction
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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