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

The KDEL retention signal used by Bejcek et al. (1989) has since been shown to be a retrieval signal-not a true retention signal-allowing for return of escaped proteins to the ER (Pelham, 1991) . There is also evidence that this signal allows some leakage of proteins to the cell surface (Zagouras and Rose, 1989) . Thus, the finding that v-sis can transform cells with this KDEL signal attached most likely indicates that an undetectable amount of the fusion protein was able to escape the ER to a more distal location, such as the cell surface, where productive autocrine interactions occurred. If protein was secreted, it likely was rapidly internalized by receptor-mediated endocytosis, and thus escaped detection. Indeed, we have experienced difficulty in immunoprecipitating and detecting wild-type v-sis protein in transformed cells due to this rapid internalization (data not shown).