Synergy between SCF or M-CSF with IL-3 or GM-CSF in FDC-P1 cells: a sensitive assay of transforming mutations of c-fms.
Stem cell factor (SCF) was found to stimulate the growth of the haemopoietic cell line FDC-P1 in synergy with either interleukin 3 (IL-3) or granulocyte-macrophage-colony stimulating factor (GM-CSF). Similarly, macrophage colony-stimulating factor (M-CSF) was shown to synergize with IL-3 or GM-CSF, following the infection of FDC-P1 cells with a recombinant retrovirus which encoded the receptor for M-CSF (M-CSFr). These results raise the possibility that signal transduction pathways which are controlled by SCF in FDC-P1 cells, can be activated by M-CSF if its receptor is illicitly expressed. FDC-P1 cells that expressed the M-CSFr were responsive to as little as 100 U/ml of M-CSF when added in combination with IL-3 or GM-CSF. This sensitive assay was used to demonstrate that transforming deletions of the C-terminal tail of the M-CSFr and two-point mutations within the same region that converted tyrosine 969 to either phenylalanine or to cysteine, allowed the mutant M-CSF receptors to synergize with IL-3 or GM-CSF in the absence of M-CSF. These mutations were found to be more evidently transforming in FDC-P1 cells than in Rat-2 fibroblasts. The possible relevance of these results to leukaemia and to gynaecological malignancies is discussed.
Baker
D A
DA
Dept of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Glover
H R
HR
Dibb
N J
NJ
D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression / Q000235:genetics; D016236:Genes, fms / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics; D012680:Sensitivity and Specificity; D019089:Stem Cell Factor; D013268:Stimulation, Chemical
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor