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

While it has been established that immature forms of the PDGF-R can be stimulated by v-sis to undergo phosphorylation within the secretory pathway (Hannink and Donoghue, 1988; Keating and Williams, 1988; Bejcek et al., 1992) , the question remains-are these interactions functional? That is, does this simple intracellular interaction between v-sis and PDGF-R contribute to acquisition of the transformed phenotype? One argument against this possibility is that the downstream effector molecules, such as PLC-3, (Kumjian et al., 1989; Meisenhelder et ai., 1989; Wahl et al., 1989; Morrison et al., 1990) , PI-3 kinase (Coughlin et ai., 1989; Kazlauskas and Cooper, 1989) , ras-GAP Kazlauskas et al., 1990) , and others, that normally interact with activated PDGF-R at the plasma membrane may not be available to the immature activated receptors present within the secretory pathway. The evidence from Bejcek et al. (1992) that indicates the intracellularly phosphorylated, immature forms of the receptor are capable of interacting with PI-3 kinase in 3T3 cells begins to address the functionality of intracellular v-sis/PDGF receptor interactions, but far from answers the question. Future studies in our lab will be aimed at examining the availability of such effector molecules within the secretory pathway, and whether they can indeed be activated intracellularly. These studies will include attempts to retarget some members of the signal transduction machinery to the early Golgi complex, to see if this will then allow sis-E1 or sis-E1-G to signal from this compartment. The results of these future studies should provide significant insight into the mechanisms of autocrine transformation.