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

Previous experiments by Lee and Donoghue (1992) suggested that the ER compartment of the secretory pathway does not support transforming interactions between v-sis and PDGF-R. One reason that the sis-G-ER ÷ construct could not productively interact with PDGF-R could be that either the ligand or the receptors had not yet undergone critical posttranslational modifications required for functional interactions and signal transduction. Such modifications may occur in the Golgi portion of the secretory pathway, particularly modifications of N-linked oligosaccharide or the addition of O-linked oligosaccharide which are largely confined to the later Golgi compartments. We have previously demonstrated that, except for disulfide bond formation which occurs in the ER very shortly after translation, further posttranslational modifications are not required for the biological activity of the v-sis protein Hannink and Donoghue, 1986b; Sauer and Donoghue, 1988) . However, extensive oligosaccharide addition and modification to PDGF-R occurs, and its importance is not clear (Keating and Williams, 1987) . Use of an early Golgi retention signal-the first transmembrane domain of the E1 glycoprotein-allowed us to begin to investigate possible autocrine interactions within the Golgi region by retaining v-sis as a fusion protein in this compartment. This retention of the v-sis oncoprotein within the early Golgi complex completely abrogated its transforming ability, and thus we conclude that productive autocrine interactions cannot occur in the early secretory pathway.