v-fps causes transformation by inducing tyrosine phosphorylation and activation of the PDGFbeta receptor.
The v-fps oncogene encodes an activated tyrosine kinase which is capable of transforming fibroblasts. In this report, we provide evidence that within a few minutes of activation of the tyrosine kinase activity of v-Fps, tyrosine phosphorylation of the platelet derived growth factor (PDGF) beta receptor is observed. Further, sustained expression of activated v-Fps results in a down-regulation of the PDGF receptor both at the level of the mRNA (approximately 4-8-fold), but even more markedly at the level of the receptor protein (> 100-fold). The kinase activity of the v-Fps oncoprotein was found to be required for both the induction of PDGF receptor tyrosine phosphorylation and ultimately the reduced receptor protein levels. Tyrosine phosphorylation of a kinase inactive PDGF receptor was also demonstrated in cells which also express v-fps, but this was not sufficient to induce transformation. Only cells expressing both v-fps and a wild type PDGF receptor were able to form colonies in soft agar. These findings suggest that wild type v-fps may use tyrosine phosphorylation of the PDGFbeta receptor to constitutively activate the kinase activity of the receptor, resulting in a sustained proliferative signal and fibroblast transformation.
Anderson
D H
DH
Saskatoon Cancer Centre Research Unit, Saskatchewan, Canada.
Ismail
P M
PM
D000595:Amino Acid Sequence; D001483:Base Sequence; D002450:Cell Communication; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015681:Fusion Proteins, gag-onc / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine
D015681:Fusion Proteins, gag-onc; D012333:RNA, Messenger; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; C068415:v-fps oncogene protein, Fujinami sarcoma virus