Regulation of mononuclear phagocyte proliferation by colony-stimulating factor-1.
Colony-stimulating factor-1 (CSF-1 or M-CSF) regulates pleiotropic developmental and functional responses of macrophages and their committed bone marrow progenitors and supports the viability of cells of the mononuclear phagocyte lineage. Its actions are mediated through its binding to cell surface CSF-1 receptors (CSF-1R) that exhibit ligand-stimulated tyrosine kinase activity. CSF-1R-induced phosphorylation of intracellular protein substrates initiates a cascade of biochemical reactions that relay signals to the cell nucleus, elicit transcription of CSF-1-responsive genes and culminate in cell division. The actions of the CSF-1R kinase can be interrupted by binding of certain monoclonal antibodies to the extracellular domain of the receptor or by agents which activate protein kinase C and accelerate receptor turnover. CSF-1R is encoded by the c-fms proto-oncogene, and specific genetic alterations, which constitutively activate the receptor kinase, provide sustained signals for cell growth leading to cell transformation. Perturbations in the structure or expression of the c-fms proto-oncogene might therefore contribute to leukemia.
Sherr
C J
CJ
Howard Hughes Medical Institute, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003115:Colony-Stimulating Factors / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000502:physiology*; D010770:Phosphotransferases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016173:Macrophage Colony-Stimulating Factor; D010770:Phosphotransferases; D016186:Receptor, Macrophage Colony-Stimulating Factor