A retrovirus encoding the v-fps protein-tyrosine kinase induces factor-independent growth and tumorigenicity in FDC-P1 cells.
There is increasing evidence that protein-tyrosine kinases play pivotal roles in the response to growth-factor signals. The cytoplasmic tyrosine kinase c-fps/fes, due to its restricted expression in hematopoietic tissue, is likely to participate in hematopoietic growth-factor signalling. We have introduced a retrovirus containing an activated fps gene (encoding P130gag-fps) into the growth factor-dependent myeloid cell line FDC-P1. Clonal cell lines were derived by selection for a marker gene coding for G418 resistance in the absence or presence of the hematopoietic growth factor IL-3. G418 resistant clones expressed P130gag-fps and its associated protein-tyrosine kinase activity and displayed either a factor-independent or IL-3 hypersensitive phenotype and were tumorigenic in syngeneic recipients. Thus, introduction of the activated v-fps gene was able to circumvent the requirement for exogenous growth factors by FDC-P1 cells. Bioassay of conditioned medium from the various clones did not detect hematopoietic growth factor activity and PCR analysis for IL-3 transcripts were negative, suggesting that growth-factor independence was achieved by a mechanism other than autocrine production of a growth factor. We suggest that P130gag-fps is acting to directly stimulate a hematopoietic growth-factor signalling pathway, perhaps one that normally involves the endogenous c-fps/fes protein-tyrosine kinase of FDC-P1 cells.
Meckling-Gill
K A
KA
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.
Yee
S P
SP
Schrader
J W
JW
Pawson
T
T
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D015681:Fusion Proteins, gag-onc / Q000235:genetics / Q000502:physiology*; D005814:Genes, Viral; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007377:Interleukin-3 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000209:etiology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic
D015681:Fusion Proteins, gag-onc; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus