Localization of the GTP-binding protein g in myelomonocytic progenitor cells is regulated by proliferation (GM-CSF, IL-3) and differentiation (TNF) signals

Philip V. Townsend*, Michael F. Crouch, Nai Ki MAK, Andrew J. Hapel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

We have examined the role of G in haemopoietic cells using the myelomonocytic progenitor cell lines FDC-P1 and WEHI-3B (JCS). During growth factor-dependent proliferation of FDC-PI cells G was found predominantly in the nucleus and associated with the plasma membrane. Following removal of growth factor, G accumulated in the cytoplasm and at the plasma membrane. Treatment of FDC-PI cells with pertussis toxin (PT) completely inhibited translocation of G to the nucleus and reduced the sensitivity of FDC-P1 cells to the proliferative effects of growth factors, indicating that translocalion of G plays a regulatory role in, but may not be essential for, cell division. G initially associated with DNA during S/G2 of the FDC-P1 cell cycle but separated from condensing chromosomes during mitosis. In contrast to FDC-P1 cells, WEHI-3B (JCS) cells proliferate in the absence of added growth factors but can be induced to differentiate by TNF-α. In proliferating JCS cells G was again associated with the nucleus but when proliferation was inhibited by TNF-α G accumulated in the cytoplasm with none detected in the nucleus. Thus the cytokine regulated accumulation of G at different intracellular sites correlated with the ability of the cell to progress through the proliferative cycle. When the tyrosine kinase inhibitor genistein was added to FDC-P1 cells prior to stimulation with IL-3 or GM-CSF, proliferation was almost completely inhibited but translocation of G was not affected, suggesting that tyrosine phosphorylation was not involved in G protein translocation but was essential for cytokine induced cell division. Cholera toxin (CT) also inhibited proliferation of FDC-P1 cells but had no effect on translocation of G to the nucleus. The near complete inhibition of cell division by genistein and CT without a corresponding effect on G movement indicates that G can be regulated independently of tyrosine kinase and adenylyl cyclase activities, respectively.

Original languageEnglish
Pages (from-to)21-30
Number of pages10
JournalGrowth Factors
Volume9
Issue number1
DOIs
Publication statusPublished - 1993

Scopus Subject Areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

User-Defined Keywords

  • Colony-stimulating factors
  • GTP-binding proteins
  • Haematopoiesis
  • Signal transduction

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