Biology and action of colony--stimulating factor-1

Mol Reprod Dev. 1997 Jan;46(1):4-10. doi: 10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V.

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 females 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 phosphates 1C, the c-cbl proto-oncogene product, and protein tyrosine phosphatase-phi are discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Embryonic and Fetal Development
  • Female
  • Helminth Proteins / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophage Colony-Stimulating Factor / physiology*
  • Macrophages / drug effects
  • Macrophages / physiology
  • Male
  • Membrane Proteins / physiology
  • Mice
  • Mice, Mutant Strains
  • Osteopetrosis / embryology
  • Osteopetrosis / genetics
  • Phosphorylation
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / physiology
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogenes
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • Signal Transduction
  • Ubiquitin-Protein Ligases*

Substances

  • Helminth Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Macrophage Colony-Stimulating Factor
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • Receptor, Macrophage Colony-Stimulating Factor
  • PTPN6 protein, human
  • PTPRO protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn6 protein, mouse
  • Ptpro protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • CBL protein, human
  • Cbl protein, mouse