Colony stimulating factor-1 (CSF-1) regulates the survival, proliferation and differentiation of mononuclear phagocytes and appears to play an important role in the formation and/or maintenance of the placenta, via its receptor, a 165 kDa tyrosine kinase which is identical to the c-fms proto-oncogene product. It is proposed to study the mechanism of CSF-1 action in vitro and in vivo. The biochemical events associated with the rapid, CSF-l induced increase in the tyrosine phosphorylation of cytoplasmic and membrane proteins in intact cells will be studied. The components involved will be identified, and if novel, their genes cloned to aid the analysis of the role of the proteins in CSF-1 signal transduction. Among other approaches, mutants of a CSF-1 responsive macrophage cell line, that are defective in their response to CSF-l, will be used to determine which of the early events are involved in particular arms of the pleiotropic response to the growth factor, particularly the mitogenic response. In addition, the distribution, function and relationship between cells synthesizing CSF-l and cells expressing the CSF-l receptor will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37CA026504-16
Application #
2087509
Study Section
Special Emphasis Panel (NSS)
Project Start
1979-07-01
Project End
1997-03-31
Budget Start
1994-06-15
Budget End
1995-03-31
Support Year
16
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Endele, Max; Loeffler, Dirk; Kokkaliaris, Konstantinos D et al. (2017) CSF-1-induced Src signaling can instruct monocytic lineage choice. Blood 129:1691-1701
Caescu, Cristina I; Guo, Xingyi; Tesfa, Lydia et al. (2015) Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21. Blood 125:e1-13
Mouchemore, Kellie A; Sampaio, Natalia G; Murrey, Michael W et al. (2013) Specific inhibition of PI3K p110ýý inhibits CSF-1-induced macrophage spreading and invasive capacity. FEBS J 280:5228-36
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Schlitzer, Andreas; McGovern, Naomi; Teo, Pearline et al. (2013) IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 38:970-83
Nandi, Sayan; Cioce, Mario; Yeung, Yee-Guide et al. (2013) Receptor-type protein-tyrosine phosphatase ? is a functional receptor for interleukin-34. J Biol Chem 288:21972-86
Yu, Wenfeng; Chen, Jian; Xiong, Ying et al. (2012) Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559, and 807. J Biol Chem 287:13694-704
Roy, Soumit; Short, Mary K; Stanley, E Richard et al. (2012) Essential role of Drosophila black-pearl is mediated by its effects on mitochondrial respiration. FASEB J 26:3822-33
Nandi, Sayan; Gokhan, Solen; Dai, Xu-Ming et al. (2012) The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation. Dev Biol 367:100-13
Hoeffel, Guillaume; Wang, Yilin; Greter, Melanie et al. (2012) Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med 209:1167-81

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