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Transformation by the v‐ fms oncogene product: An analog of the CSF‐1 receptor
Author(s) -
Rettenmier Carl W.,
Jackowski Suzanne,
Rock Charles O.,
Roussel Marline F.,
Sherr Charles J.
Publication year - 1987
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240330205
Subject(s) - phospholipase c , second messenger system , tyrosine kinase , receptor tyrosine kinase , tyrosine phosphorylation , phosphatidylinositol , gene product , biology , receptor , microbiology and biotechnology , diacylglycerol kinase , signal transduction , chemistry , biochemistry , protein kinase c , gene , gene expression
The product of the c‐ fms proto‐oncogene is related to, and possibly identical with, the receptor for the macrophage colony‐stimulating factor, M‐CSF (CSF‐1). Unlike the product of the v‐ erb B oncogene, which is a truncated version of the EGF receptor, the glycoprotein encoded by the v‐ fms oncogene retains an intact extracellular ligand‐binding domain so that cells transformed by v‐ fms express CSF‐1 receptors at their surface. Although fibroblasts susceptible to transformation by v‐ fms generally produce CSF‐1, v‐ fms ‐mediated transformation does not depend on an exogenous source of the growth factor, and neutralizing antibodies to CSF‐1 do not affect the transformed phenotype. An alteration of the v‐ fms gene product at its extreme carboxyl‐terminus represents the major structural difference between it and the c‐ fms ‐coded glycoprotein and may affect the tyrosine kinase activity of the v‐ fms ‐coded receptor. Consistent with this interpretation, 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. Cells transformed by v‐ fms have a constitutively elevated specific activity of a guanir.c nucleotide‐dependent, phosphatidylinositol‐4,5‐diphosphate‐specific phospholipase C. We speculate that the tyrosine kinase activity of the v‐ fms /c‐ fms gene products may be coupled to this phospholipase C, possibly through a G regulatory protein, thereby increasing phosphatidylinositol turnover and generating the intracellular second messengers diacylglycerol and inositol triphosphatc.