Cell cycle control of PDGF-induced Ca2+ signaling through modulation of sphingolipid metabolism

Alessandro Fatatis, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The effects of growth factors have been shown to depend on the position of a cell in the cell cycle. However, the physiological basis for this phenomenon remains unclear. Here we show that the majority of both CEINGE clone3 (cl3) and human embryonic kidney 293 cells, when arrested in a quiescent phase (G0), responded to platelet-derived growth factor BB (PDGF- BB) with non-oscillatory Ca2+ signals. Furthermore, the same type of Ca2+ response was also observed in CEINGE cl3 cells (and to a lesser extent in HEK 293 cells) blocked at the G1/S boundary. In contrast, CEINGE cl3 cells synchronized in early G1 or released from G1/S arrest responded in an oscillatory fashion. This cell cycle-dependent modulation of Ca2+ signaling was not observed on epidermal growth factor and G-protein-coupled receptor stimulation and was not due to differences in the expression of PDGF receptors (PDGFRs) during the cell cycle. We demonstrate that inhibition of sphingosine-kinase, which converts sphingosine to sphingosine-1-phosphate, caused G0 as well as G1/S synchronized cells to restore the oscillatory Ca2+ response to PDGF-BB. In addition, we show that the synthesis of sphingosine and sphingosine-1-phosphate is regulated by the cell cycle and may underlie the differences in Ca2+ signaling after PDGFR stimulation.

Original languageEnglish (US)
Pages (from-to)1291-1301
Number of pages11
JournalFASEB Journal
Volume13
Issue number11
DOIs
StatePublished - 1999

Keywords

  • DHS
  • DMS
  • Epidermal growth factor
  • PDGF

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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