THE CSF-1 RECEPTOR IS RELATED TO THE C-FMS PROTO-ONCOGENE PRODUCT (GROWTH FACTORS, RECEPTORS, TYROSINE KINASES, PHOSPHORYLATION)

Abstract

The development of mature blood cells is dependent on a population of precursor cells which are stimulated to proliferate and differentiate by specific regulatory proteins. The colony stimulating factor, CSF-1, can stimulate the proliferation, differentiation and survival of cells of the mononuclear phagocytic lineage. The pleiotropic response to CSF-1 is mediated via a 165 kDa cell surface receptor with an associated tyrosine kinase activity. The v-fms oncogene product of the Susan McDonough strain of feline sarcoma virus (SM-FeSV) is derived from the cellular proto-oncogene c-fms. The feline c-fms-encoded protein is a glycoprotein of 170 kDa. It is found on mature cat macrophages and has an associated tyrosine kinase activity.;Rabbit antisera to a recombinant v-fms-encoded polypeptide precipitated the feline c-fms product and cross-reacted with a 165 kDa glycoprotein from mouse macrophages. This putative murine c-fms gene product specifically bound murine CSF-1 and in the presence of the growth factor was phosphorylated on tyrosine residues. These data suggest that the murine c-fms proto-oncogene product and the CSF-1 receptor are functionally and antigenically related molecules.;Cells transformed by the Susan McDonough strain of the feline sarcoma virus (SM-FeSV) express a v-fms-encoded glycoprotein at the cell surface which specifically binds murine CSF-1. A monoclonal antibody to a v-fms-encoded epitope can compete for this binding and chemical cross-linking demonstrated that CSF-1 is bound to the v-fms gene product. The SM-FeSV lines were found to secrete CSF-1, but growth of the transformed cells was not inhibited by antibodies to the v-fms gene product or to the growth factor. Tyrosine phosphorylation of the v-fms is observed in the absence of CSF-1 and could not be enhanced by addition of the growth factor. These data further support the hypothesis that the c-fms proto-oncogene product is related, if not identical, to the CSF-1 receptor, and suggest that the v-fms-encoded kinase functions in the absence of an exogenous growth factor.