Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of Src and Ras actions

Norbert E. Kremer, Gabriella D'Arcangelo, Sheila M. Thomas, Michael DeMarco, Joan S. Brugge, Simon Halegoua

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

We have investigated the roles of pp60c-src and p21c-ras proteins in transducing the nerve growth factor (NGF) and fibroblast growth factor (FGF) signals which promote the sympathetic neuronlike phenotype in PC12 cells. Neutralizing antibodies directed against either Src or Ras proteins were microinjected into fused PC12 cells. Each antibody both prevented and reversed NGF- or FGF-induced neurite growth, a prominent morphological marker for the neuronal phenotype. These data demonstrate the involvement of both pp60c-src and p21c-ras proteins in NGF and FGF actions in PC12 cells, and establish a physiological role for the pp60c-src tyrosine kinase in signal transduction pathways initiated by receptor tyrosine kinases in these cells. Additional microinjection experiments, using PC12 transfectants containing inducible v-src or ras oncogene activities, demonstrated a specific sequence of Src and Ras actions. Microinjection of anti-Ras antibody blocked v-src-induced neurite growth, but microinjection of anti-Src antibodies had no effect on ras oncogene-induced neurite growth. We propose that a cascade of Src and Ras actions, with Src acting first is a significant feature of the signal transduction pathways for NGF and FGF. The Src-Ras cascade may define a functional cassette in the signal transduction pathways used by growth factors and other ligands whose receptors have diverse structures and whose range of actions on various cell types include mitogenesis and differentiation.

Original languageEnglish (US)
Pages (from-to)809-819
Number of pages11
JournalJournal of Cell Biology
Volume115
Issue number3
DOIs
StatePublished - Jan 1 1991

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Fibroblast Growth Factors
PC12 Cells
Nerve Growth Factor
ras Proteins
Signal Transduction
Microinjections
Neurites
ras Genes
Anti-Idiotypic Antibodies
Growth
src Genes
Phenotype
src-Family Kinases
Receptor Protein-Tyrosine Kinases
Neutralizing Antibodies
Intercellular Signaling Peptides and Proteins
Ligands
Antibodies

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Kremer, Norbert E. ; D'Arcangelo, Gabriella ; Thomas, Sheila M. ; DeMarco, Michael ; Brugge, Joan S. ; Halegoua, Simon. / Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of Src and Ras actions. In: Journal of Cell Biology. 1991 ; Vol. 115, No. 3. pp. 809-819.
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Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of Src and Ras actions. / Kremer, Norbert E.; D'Arcangelo, Gabriella; Thomas, Sheila M.; DeMarco, Michael; Brugge, Joan S.; Halegoua, Simon.

In: Journal of Cell Biology, Vol. 115, No. 3, 01.01.1991, p. 809-819.

Research output: Contribution to journalArticle

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