Biology and action of colony-stimulating factor-1

E. Richard Stanley, Karen L. Berg, Douglas B. Einstein, Pierre S.W. Lee, Fiona J. Pixley, Yun Wang, Yee Guide Yeung

Research output: Contribution to journalArticle

310 Scopus citations

Abstract

Colony-stimulating factor-1 (CSF-1), also known as macrophage colony- stimulating factor, controls the survival, proliferation, and differentiation of mononuclear phagocytes and regulates cells of the female reproductive tract. It appears to play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, and myeloid and lymphoid tissues. Through alternative mRNA splicing and differential post-translational proteolytic processing, CSF-1 can either be secreted into the circulation as a glycoprotein or chondroitin sulfate-containing proteoglycan or be expressed as a membrane-spanning glycoprotein on the surface of CSF-1-producing cells. Studies with the op/op mouse, which possesses an inactivating mutation in the CSF-1 gene, have established the central role of CSF-1 in directly regulating osteoclastogenesis and macrophage production. CSF-1 appears to preferentially regulate the development of macrophages found in tissues undergoing active morphogenesis and/or tissue remodeling. These CSF-1 dependent macrophages may, via putative trophic and/or scavenger functions, regulate characteristics such as dermal thickness, male fertility, and neural processing. Apart from its expression on mononuclear phagocytes and their precursors, CSF-1 receptor (CSF-1R) expression on certain nonmononuclear phagocytic cells in the female reproductive tract and studies in the op/op mouse indicate that CSF-1 plays important roles in female reproduction. Restoration of circulating CSF-1 to op/op mice has preliminarily defined target cell populations that are regulated either humorally or locally by the synthesis of cell-surface CSF-1 or by sequestration of the CSF-1 proteoglycan. The CSF-1R is a tyrosine kinase encoded by the c-fms proto- oncogene product. Studies by several groups have used cells expressing either the murine or human CSF-1R in fibroblasts to pinpoint the requirement of kinase activity and the importance of various receptor tyrosine phosphorylation sites for signaling pathways stimulated by CSF-1. To investigate post-CSF-1R signaling in the macrophage, proteins that are rapidly phosphorylated on tyrosine in response to CSF-1 have been identified, together with proteins associated with them. Studies on several of these proteins, including protein tyrosine phosphatase 1C, the c-cbl proto-oncogene product, and protein tyrosine phosphatase-phi are discussed.

Original languageEnglish (US)
Pages (from-to)4-10
Number of pages7
JournalMolecular Reproduction and Development
Volume46
Issue number1
DOIs
StatePublished - Jan 1 1997

Keywords

  • colony-stimulating factor
  • growth factor
  • signal transduction

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

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    Stanley, E. R., Berg, K. L., Einstein, D. B., Lee, P. S. W., Pixley, F. J., Wang, Y., & Yeung, Y. G. (1997). Biology and action of colony-stimulating factor-1. Molecular Reproduction and Development, 46(1), 4-10. https://doi.org/10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V