This study is directed toward understanding the biochemistry, action, and production of a subclass of the colony-stimulating factor (CSF) that stimulates mononuclear phagocyte proliferation (CSF-1). Mononuclear phagocytes exhibit a pleiotropic response to CSF-1. CSF-1 stimulates their survival, proliferation, and differentiation. It rapidly induces striking morphological changes and stringently regulates protein turnover by increasing the rate of protein synthesis and decreasing the rate of protein degradation. The pleiotropic response to CSF-1 is mediated by a specific cell surface receptor. Chemical crosslinking studies indicate that the receptor is a single polypeptide chain of Mr 160,000 that is not disulfide-bonded to any other molecule. These findings have been confirmed by purification and characterization of the receptor of a macrophage cell line. The purified receptor is a protein kinase that autophosphorylates in tyrosine on binding purified CSF-1. In collaboration with others it was shown that the CSF-1 receptor is immunologically and functionally related to the cellular oncogene, c-fms. In isolated membrane preparations, the CSF-1 receptor mediates increases in the phosphorylation of several membrane proteins including a protein with the molecular weight of the receptor itself. The number of membrane proteins phosphorylated varies with cell type. More proteins are phosphorylated in cells requiring CSF-1 for growth than on receptor-bearing cells capable of autonomous growth. In another collaboration, a hybridoma cell line that produces high-affinity monoclonal antibody to murine CSF-1 has been obtained. This antibody can be used to rapidly purify murine and human CSF-1. (HF)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026504-07
Application #
3167337
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1979-07-01
Project End
1989-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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