Cloning of the murine c-fgr proto-oncogene cDNA and induction of c-fgr expression by proliferation and activation factors in normal bone marrow-derived monocytic cells

Normal murine bone marrow-derived monocytic cells were found to contain transcripts for c-fgr and hck, two members of the src family of proto-oncogene tyrosine kinases. While hck transcripts were increased only in response to bacterial lipopolysaccaride (LPS), expression of c-fgr was transiently induced both by the monocyte/macrophage proliferative stimulus CSF-1 as well as by signals which activate monocytic cells to functional states (granulocyte-macrophage colony stimulating factor (GM-CSF), LPS, and gamma interferon). These data suggest that these highly related tyrosine kinases may differentially mediate the effects of distinct monocyte/macrophage stimuli; and, that the c-fgr proto-oncogene in particular, which in normal cells is selectively expressed in monocytes, may play a pivotal functional role in these cells. A 2.2 kb cDNA clone, containing a 1551 base pair open reading frame encoding a protein with all of the hallmarks of a protein-tyrosine kinase, was isolated from a cDNA library made from RNA of CSF-1-stimulated bone marrow-derived monocytic cells. This clone had the highest homology to v-fgr and likely encodes the murine c-fgr transcript expressed by normal monocytes. However, when compared to sequences previously reported for human c-fgr derived from EBV-transformed B cells and heterogeneous peripheral blood cells, the c-fgr cDNA derived from normal murine monocytic cells differed significantly in sequence from amino acids 12-62 in the amino terminal domain of the protein which may mediate the substrate specificity and subcellular location of the src family of protein-tyrosine kinases.