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.
Yi
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TL
Department of Cell Biology, University of New Mexico School of Medicine, Albuquerque 87131.
Willman
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CL
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004247:DNA / Q000032:analysis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D011519:Proto-Oncogenes; D014158:Transcription, Genetic; D019061:src-Family Kinases
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D008070:Lipopolysaccharides; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases