Uncoupling of the proliferation and differentiation signals mediated by the murine macrophage colony-stimulating factor receptor expressed in myeloid FDC-P1 cells

R. P. Bourette, G. M. Myles, K. Carlberg, A. R. Chen, L. R. Rohrschneider

Research output: Contribution to journalArticlepeer-review

Abstract

The macrophage colony-stimulating factor (M-CSF) regulates proliferation and differentiation of cells belonging to the monocytic lineage. We have investigated the nature and origin of the proliferation and differentiation signals derived from the M-CSF receptor (Fms) by mutating Fms at the four tyrosine autophosphorylation sites and examining their biological effects in an FDC-Pt clone. Wild-type Fms stimulated both growth and differentiation of FDC-P1 cells in response to M-CSF stimulation. In contrast, both proliferation and differentiation were differentially disrupted by mutations affecting the fear tyrosine autophosphorylation sites. These analyses revealed that: (a) none of the four autophosphorylation sites studied (Y697, Y706, Y721, and Y807) were essential for M-CSF-dependent proliferation of the FDC-P1 clone; (b) Y697, Y706, and Y721 sites, located in the kinase insert region of Fms, were not necessary for differentiation, but their presence augmented this process; (c) mutation of the Y807 site totally abrogated the differentiation of the FDC-P1 clone and simultaneously increased the rate of M-CSF-dependent proliferation; and (d) conversely, increasing the intracellular cAMP level blocked the growth signal in the FDC-P1 clone but had no effect on differentiation. These results suggest that autophosphorylation of Fms at the Y807 site controls the balance between signals for growth and differentiation.

Original languageEnglish (US)
Pages (from-to)631-645
Number of pages15
JournalCell Growth and Differentiation
Volume6
Issue number6
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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