Cyclic adenosine monophosphate can convert epidermal growth factor into a differentiating factor in neuronal cells

H. Yao, K. Labudda, C. Rim, P. Capodieci, M. Loda, P. J.S. Stork

Research output: Contribution to journalArticle

55 Scopus citations


The rat pheochromocytoma (PC12) cell line is a model for studying the mechanism of growth factor action. Both epidermal growth factor and nerve growth factor stimulate mitogen-activated protein (MAP) kinase in these cells. Recent data suggest that the transient activation of MAP kinase may trigger proliferation, whereas sustained activation triggers differentiation in these cells. We have tested this model by asking whether agents that stimulate MAP kinase without inducing differentiation can act additively to trigger differentiation. Neither forskolin nor epidermal growth factor can stimulate differentiation, yet both activate MAP kinase in these cells. Together, their actions on MAP kinase are synergistic. Cells treated with both agents differentiate, measured morphologically and by the induction of neural-specific genes. We propose that cellular responses to growth factor action are dependent not only on the activation of growth factor receptors by specific growth factors but on synchronous signals that may elevate MAP kinase levels within the same cells.

Original languageEnglish (US)
Pages (from-to)20748-20753
Number of pages6
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Jan 1 1995


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this