Our previous studies have demonstrated the importance of human sis/platelet-derived growth factor (PDGF)-2 gene deregulation in its activation as an oncogene in cells responsive to PDGF stimulation. Current studies have focused on the structure, regulation and function of this gene. We have shown that human tumor cells arising from PDGF-responsive cell types express sis/PDGF-2 mRNA and mitogenically active sis/PDGF-2 homodimers. Utilizing cDNA cloning, Sl nuclease mapping, and primer extension techniques, the normal human sis/PDGF-2 transcriptional unit has been defined. These studies also suggested the presence of transcriptional and translational regulatory signals within the sis/PDGF-2 locus, and have provided an approach for elucidating mechanisms by which this gene is controlled. Knowledge that the v-sis oncogene encodes a PDGF-related product whose transforming activity requires functional interaction with the PDGF receptor has suggested the importance of identifying the active site of the v-sis translational product. Site-directed mutagenesis of v-sis has localized an 89-codon stretch as its minimum transforming region and has shown a requirement for each of eight cysteine codons within the region for proper folding of the v-sis gene product. These studies have also predicted three testable models for the active conformation of this protein and represent an important step in identifying the receptor binding domain of this oncogenic growth factor.
