Transforming growth factor β modulates epidermal growth factor-induced phosphoinositide metabolism and intracellular calcium levels

L. L. Muldoon, K. D. Rodland, B. E. Magun

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Transforming growth factor β (TGFβ) alters the cellular response to epidermal growth factor (EGF) in a number of systems, but the underlying mechanisms for these alterations are largely unknown. We have examined second messenger formation in Rat-1 cells following treatment with EGF and/or TGFβ to determine whether the ability of TGFβ to potentiate some EGF-stimulated processes might be mediated by TGFβ-induced alterations in the signal transduction mechanism. Incubation of serum-deprived confluent Rat-1 cells with 10 ng/ml TGFβ resulted in a marked elevation of cellular inositol trisphosphate and inositol tetrakisphosphate levels, which were maximal at 4 h and maintained for at least 8 h. The effect of TGFβ on levels of inositol trisphosphate and inositol tetrakisphosphate was blocked by actinomycin D, suggesting that RNA synthesis was required for the TGFβ effect. While EGF stimulation induced a rapid and transient (5 min) rise in inositol phosphate levels in control cells, the EGF effect was considerably increased, both in magnitude and duration, by TGFβ treatment. Measurement of intracellular free Ca2+ with fura-2 demonstrated that TGFβ treatment markedly increased the EGF-stimulated rise in free Ca2+ and increased the duration of the response. The positive effects of TGFβ on EGF stimulation could not be explained on the basis of increased EGF binding to cells. We conclude that TGFβ treatment can both activate phosphatidylinositol turnover independently and also sensitize Rat-1 cells to stimulation by EGF.

Original languageEnglish (US)
Pages (from-to)5030-5033
Number of pages4
JournalJournal of Biological Chemistry
Volume263
Issue number11
StatePublished - 1988

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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