Human colony stimulating factor-1 receptor activates the C-raf-1 proto-oncogene kinase

The proto-oncogene c-raf-1 encodes a 74 kD serine/threonine kinase. Recently, it has been shown that Raf kinase activity is stimulated by platelet derived growth factor (PDGF) treatment of receptor bearing cells, and that p74 is a direct substrate for PDGF receptor. CSF-1 treatment of BeWo cells, a human choriocarcinoma cell line, and mouse NIH 3T3 cells expressing a transfected human CSF-1 receptor cDNA, was associated with a 3-4 fold increase in phosphorylation of a 74 kD protein immunoprecipitated with affinity purified Raf-1 antibody. The kinase activity of p74 was increased 2-3 fold against two exogenous substrates following CSF-1 treatment of the transfected cells. These observations suggest that Raf-1 protein is a downstream second messenger molecule in CSF-1 mediated signal transduction.