THE BIOLOGY AND ACTION OF COLONY-STIMULATING FACTOR-I

Colony stimulating factor 1 (CSF-1) is a growth factor for mononuclear phagocytic cells. Through alternative mRNA splicing and differential post-translational proteolytic processing, CSF-1 can either be secrete d into the circulation as a glycoprotein or chondroitin sulfate-contai ning proteoglycan or expressed as a membrane-spanning glycoprotein on the surface of synthesizing cells. The discovery that the osteopetroti c (op/op) mutant mouse possesses an inactivating mutation in the CSF-1 gene has greatly contributed to our understanding of CSF-1 biology, C SF-1 directly regulates some non-mononuclear phagocytic cells that exp ress the CSF-1 receptor tyrosine kinase, but is not required for their development. However, it directly regulates the development and maint enance of tissue macrophage subpopulations that appear to have importa nt trophic and/or scavenger roles in tissue morphogenesis and function . Depending on the tissue, this regulation may be local (via the cell- surface form) localized (via the sequestered proteoglycan form) or hum oral. It appears that the CSF-1 dependent tissue macrophage subpopulat ions, via their effects on other cell types, can significantly affect functions in tissues as diverse as testis, brain and skin, and their a bsence in op/op mice may explain the pleiotropy of the op/op phenotype . To investigate post-CSF-1 receptor signaling in the macrophage, proc edures have been developed for the purification and sequence determina tion of the proteins that are rapidly phosphorylated on tyrosine in re sponse to CSF-1. Several have been identified and the behavior of one of them, protein tyrosine phosphatase 1C (PTP1C), is discussed.