Phosphatidylcholine signaling in response to CSF-1

Suzanne Jackowski, Xiang Xi Xu, Charles O. Rock

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The formation of cell membrane following CSF-1 stimulation of a macrophage cell line is coordinated with cell cycle progression. The majority of membrane phospholipid accumulates during the S phase and results from cell-cycle dependent oscillations in the rates of phosphatidylcholine biosynthesis and degradation. Both synthesis and degradation are enhanced during the G 1 phase, resulting in a high rate of phosphatidylcholine turnover. Degradation of phosphatidylcholine after CSF-1 stimulation is mediated by a phospholipase C, and the release of diacylglycerol during G 1 phase is biphasic. The degradation essentially stops during the S phase, thus allowing biosynthesis to supply the necessary membrane for cell division and doubling. The degradation of phosphatidylcholine during G 1 signals the downstream activation of c-fos and junB transcription and can be mimicked by incubation of the macrophage cells with exogenous bacterial phospholipase C. in contrast, the expression of c-myc transcripts normally associated with CSF-1 stimulation is severely compromised in phospholipase C-treated cells, indicating that the diacylglycerol signals a pathway distinct from the pathway that governs c-myc activation. Constitutive expression of c-myc complements phospholipase C activity and permits the growth of cells in the presence of exogenous bacterial enzyme and the absence of CSF-1. Protein kinase C is not required to mediate the diacylglycerol signal that supports cell growth. GTP exchange on Ras is not enhanced, and MAP kinase activity is not stimulated in response to phosphatidylcholine degradation by exogenous phospholipase C. The 85 kDa cytoplasmic phospholipase A 2 is activated, however, as well as a novel protein we have called p96. Rapid serine phosphorylation of p96 follows stimulation of cells with either CSF-1 or exogenous phospholipase C. Analysis of the murine cDNA encoding p96 reveals an amino-terminal domain with significant similarity to the amino-terminal domain of the Drosophila-disabled gene product and a carboxy-terminal domain containing proline-rich sequences characteristic of SH3 binding regions. The sequence of p96 suggests an interactive role for this unique protein in the CSF-1 signal transduction cascade.

Original languageEnglish (US)
Pages (from-to)24-30
Number of pages7
JournalMolecular Reproduction and Development
Volume46
Issue number1
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Keywords

  • CSF-1
  • phospholipase
  • signal transduction

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

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