Abstract
The viral (v)-sis oncogene encodes a protein (p28sis) that is structurally homologous to platelet-derived growth factor (PDGF). We have shown that simian sarcoma virus (SSV)-transformed cells containing the v-sis oncogene release a Mr 20,000 substance that is recognized by antisera to synthetic peptide sequences contained in p28sis. Medium conditioned by SSV-transformed cells competes with 125I-labeled PDGF for specific PDGF receptor sites, initiates DNA synthesis, and stimulates tyrosine phosphorylation of the PDGF receptor when added to normal cells. When normal cells are co-cultured with SSV-transformed cells, the PDGF receptors of the normal cells are down-regulated by factors released from the transformed cells. Thus, SSV-transformed cells release material that is functionally similar to PDGF. We have used anti-phosphotyrosine antibodies to purify PDGF receptors and to detect PDGF-stimulated receptors in normal cells. SSV-transformed cells have no PDGF receptors detectable by these antibodies or by 125I-labeled PDGF binding studies. However, when SSV-transformed cells are exposed to suramin, a compound that blocks binding of PDGF to its receptors, the receptors reappear on the cell surface and within 8 hr are present at the same levels as in control cells. These "new" receptor sites can be phosphorylated in response to PDGF. Thus, the absence of PDGF receptors in SSV-transformed cells is due to down-regulation of the receptors by an autocrine mechanism that can be blocked by suramin.
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Selected References
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