Transforming mechanism of the feline sarcoma virus encoded v-fms oncogene product.
The v-fms oncogene product encoded by the McDonough strain of feline sarcoma virus (SM-FeSV) is a transmembrane glycoprotein which belongs to the tyrosine kinase receptor family. The cellular counterpart, the c-fms product, is the receptor for macrophage colony stimulating factor (M-CSF or CSF-1). The v-fms and the c-fms product differ structurally only in seven point mutations and in their C-terminal domains. We have corrected the published sequence of the v-fms product and found that the new C-terminal end contains a threonine phosphorylation site (Thr939). This site is phosphorylated in vivo leading to an enhancement of the v-fms-specific tyrosine kinase activity. The extracellular domain of the v-fms product contains 11 N-glycosylation sites. Glycosylation and transport of the v-fms molecules to the plasma membrane are prerequisites for the transforming potential of the virus. Phosphorylation of the v-fms molecules in tyrosine, serine and threonine residues takes place only at the plasma membrane. Coexpression showed that the overexpression of M-CSF and c-fms in fibroblasts leads to cell transformation by an autocrine loop mechanism. This interaction between M-CSF and the c-fms protein also takes place at the plasma membrane. To study the v-fms transforming mechanisms, we have expressed the v-fms oncogene in chicken fibroblasts which are free of the cross-reactive M-CSF. The expression of the v-fms oncogene alone did not cause transformation. However, upon addition of M-CSF, these cells became completely transformed.(ABSTRACT TRUNCATED AT 250 WORDS)
Tamura
T
T
Institut für Virologie, Justus-Liebig-Universität Giessen, Germany.
Hadwiger-Fangmeier
A
A
Simon
E
E
Smola
U
U
Geschwill
H
H
Schütz
B
B
Trouliaris
S
S
Boscheck
B
B
Niemann
H
H
Bauer
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D002471:Cell Transformation, Neoplastic; D016236:Genes, fms; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008969:Molecular Sequence Data; D016281:Oncogene Protein gp140(v-fms) / Q000235:genetics* / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D015398:Signal Transduction
D016281:Oncogene Protein gp140(v-fms); D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor