Transforming growth factor β and epidermal growth factor alter calcium influx and phosphatidylinositol turnover in Rat-1 fibroblasts

L. L. Muldoon, K. D. Rodland, Bruce Magun

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67 Scopus citations


Transforming growth factor type β (TGFβ) alters the cellular response to epidermal growth factor (EGF) for a variety of processes ranging from early transport activities and gene transcription to mitogenesis. In order to test the hypothesis that altered signal transduction mechanisms may mediate both the transforming effects of TGFβ and the modulation of EGF-stimulated processes by TGFβ, we have examined second messenger levels in response to growth factor treatment. The addition of EGF or prolonged treatment with TGFβ increased the rate of 45Ca influx in serum-deprived, confluent Rat-1 cells, while the addition of EGF to TGFβ-pretreated cells produced an additive increase in Ca2+ influx. The stimulation of Ca2+ influx by TGFβ was only observed at incubation times greater than 1 h and was inhibited by inclusion of actinomycin D, suggesting that a newly transcribed gene product was required for the observed response to TGFβ. Both EGF and TGFβ displayed similar time and concentration dependencies for stimulation of Ca2+ influx and for accumulation of inositol trisphosphate (IP3). The increase in IP3 accumulation in response to either EGF or TGFβ required the presence of extracellular Ca2+, and the observed concentration dependencies were similar for the stimulation of phosphatidylinositol turnover and Ca2+ influx. The EGF- and TGFβ-stimulated increased in Ca2+ influx could be blocked by cobalt, cadmium, and [ethylenebis(oxyethylenenitrilo)] tetraacetic acid, but not by specific Ca2+ channel blockers such as nifedipine or verapamil, suggesting that these growth factors do not act via L-type voltage-sensitive calcium channels. Those calcium blockers which inhibited Ca2+ influx also inhibited inositol phosphate release. These data, taken together, indicate that Ca2+ influx and inositol phosphate release are coupled in Rat-1 cells and suggest that influx of Ca2+ from the extracellular medium is responsible for the changes in IP3 accumulation observed in response to both EGF and TGFβ.

Original languageEnglish (US)
Pages (from-to)18834-18841
Number of pages8
JournalJournal of Biological Chemistry
Issue number35
StatePublished - 1988

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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