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

Since v-sis-transformed ceils express both v-sis protein and PDGF receptors, there exists the possibility that these two proteins can interact as they pass simultaneously through the secretory pathway. Keating and Williams (1988) reported the detection of PDGF receptors that are activated intracellularly in v-sis-transformed cells. These receptors were of an immature form, as determined by their molecular mass (160 kD) and lack of glycosylation (Huang and Huang, 1988; Keating and Williams, 1988) , and are rapidly degraded after stimulation by v-sis (Keating and Williams, 1988; Bejcek et al., 1992) . High concentrations of antisera to PDGF were shown to be unable to reverse transformation of NRK cells. Also, high levels of exogenously added v-sis protein have not been shown to cause transformation of NRK cells (Bejcek et al., 1989) . Both of these observations suggest that an intracellular autocrine mechanism may exist. These same researchers attached a six-amino acid ER-retention signal, SEKDEL, to the v-sis protein and observed morphological transformation of cells expressing this fusion protein. No secreted fusion protein was detectable. Bejcek and coworkers (1992) also have shown that v-sis, but not endogenously expressed PDGF-A homodimers, can activate PDGF receptors intracellularly; thus the capacity of v-sis to act intracellularly may underlie its mechanism of transformation.