Rosalba Sacca

The c-fms gene product is related, and possibly identical, to the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. Using antisera to a recombinant v-fms--coded polypeptide, glycoproteins encoded by the human c-fms locus were detected in mononuclear cells from normal peripheral blood and in promyelocytic HL-60 cells 24 h after induction of monocytic differentiation with phorbol ester. The 150-kD human c-fms--coded glycoprotein was expressed at the cell surface, was active as a tyrosine-specific protein kinase in vitro, and shared primary structural features with the product of the feline retroviral v-fms oncogene. A biochemically indistinguishable glycoprotein was detected in human choriocarcinoma cell lines. Like peripheral blood mononuclear cells and phorbol ester-treated HL-60 cells, the choriocarcinoma cells expressed high affinity binding sites for human CSF-1. In addition to serving as a lineage specific growth factor in hematopoiesis, CSF-1 may play a role in normal trophoblast development.

Cells transformed by the McDonough strain of feline sarcoma virus (SM-FeSV) express a v-fms-encoded glycoprotein whose expression at the cell surface correlates with the transformed phenotype. The mouse mononuclear phagocyte growth factor CSF-1 specifically binds to SM-FeSV-transformed cells at high-affinity sites indistinguishable from those detected on normal feline macrophages. A monoclonal antibody to a v-fms-encoded epitope competed for CSF-1 binding to SM-FeSV-transformed cells, and chemical crosslinking demonstrated that murine CSF-1 bound to the v-fms gene product at the cell surface. Although SM-FeSV-transformed fibroblast lines were found to secrete CSF-1, the growth of transformed cells was not affected by antibodies to the v-fms gene product or to the growth factor. Tyrosine phosphorylation of the v-fms products in membranes was observed in the absence of CSF-1 and was not enhanced by addition of the murine growth factor. The data support the hypothesis that the c-fms protooncogene product is related, and possibly identical, to the CSF-1 receptor and suggest that the v-fms-encoded kinase functions in the absence of an exogenous growth factor.