The sis gene and PDGF.

The aberrant expression of a protein that is involved in normal growth regulatory pathways can cause cell transformation. One of the best examples of this phenomenon is the transformation of fibroblasts by the simian sarcoma virus (SSV). An oncogene (v-sis) of this virus encodes a protein whose amino acid sequence is highly homologous to one of the subunits of a mesenchymal cell mitogen, platelet-derived growth factor (PDGF). How does expression of the v-sis or related genes transform cells? Clearly, this process uses biochemical pathways involved in the normal actions of growth factors. For example, the v-sis-encoded protein appears to act through cellular PDGF receptors. The biochemical consequences of PDGF receptor activation include increased tyrosine kinase activity, enhanced expression of a set of genes associated with cell proliferation, the dramatic alteration in cellular cytoskeleton, a rapid turnover of membrane phospholipids and the commitment of the cell to proceed through a series of responses culminating in the replication of DNA. An important issue is whether, in SSV transformed cells, these biochemical pathways are simply overstimulated by an abundance of self-made growth factor, or are there qualitative alterations in the pathways that are unique to these cells. Several specific related questions are addressed in this discussion: Is the protein encoded by the v-sis gene functionally identical to PDGF? Does the v-sis-encoded protein act at the cell surface or at intracellular sites? In the action of PDGF-like compounds, what are the biochemical steps distal to receptor stimulation?(ABSTRACT TRUNCATED AT 250 WORDS)