The v-sis oncoprotein loses transforming activity when targeted to the early Golgi complex

Autocrine transformation (Sporn and Todaro, 1980) oc-curs when the same cell expresses PDGF receptors as well as the v-sis protein. In this situation, there also exists the possibility of intracellular ligand/receptor interactions within the secretory pathway (Betsholtz et al., 1986) . The secretory pathway consists of functionally distinct compartments, including the endoplasmic reticulum (ER) and the entire Golgi apparatus, consisting of the cis-Golgi network, the cis-, medial-, and trans-Golgi cisternae, as well as the trans-Golgi network (TGN) t (Macharner, 1993; Pelham, 1991) . Determination of the site of autocrine ligand/receptor interactions has distinct implications for the treatment of human cancers that exhibit autocrine activation of signal transduction pathways. If autocrine interactions only occur on the cell surface, then transformed cells should be responsive to treatment with exogenous substances that disrupt these interactions. However, if such interactions occur intracellularly, such as in the ER or the Golgi complex, then addition of such antagonism will not be sufficient to revert transformation. Thus, it is of vital importance, both from a clinical and a molecular standpoint, to understand fully the mechanism and cellular location of autocrine interactions between ligands and receptors. There exists considerable controversy over the biological significance of intracellular interactions between v-sis and the PDGF-receptor. It has been demonstrated that mitogenesis can be blocked in some sis-transformed cells by treating them with antibodies against PDGF (Huang et al., 1984) . While these results indicate that cell surface interactions between the v-sis protein and PDGF receptors are important in the transformation process, these same researchers demonstrated that some sis-transformed cells did not detectably secrete v-sis protein, and anti-PDGF antibody did not affect transformation. This implies that an intracellular mechanism of autocrine transformation may also exist. Other researchers have reported that in normal cells, PDGF only activates receptors present on the cell surface, but that in sis-transformed cells, intracellular receptors are activated and undergo autophosphorylation in an autocrine fashion (Keating and Williams, 1988; Bejcek et al., 1992) . There is also evidence that E5, the transforming protein of bovine papillomavirus, can interact with immature, intracellular forms of PDGF receptors, stimulating their autophosphorylation activity (Goldstein et al., 1992; Petti and DiMaio, 1992; Cohen et al., 1993) .