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

The membrane-anchor region of sis-TGN38 consists of 59 amino acids, containing the transmembrane domain and cytoplasmic tail of TGN38, a Type I-oriented protein which was isolated from rat liver Golgi membranes (Luzio et al., 1990) and is normally localized to the TGN (Ladinsky and Howell, 1992; Bos et al., 1993; Reaves et al., 1993) . A tyrosine-containing motif, Tyr-Gln-Arg-Leu (YQRL), in the COOH-terminal domain of TGN38, has been shown to be essential for TGN localization (Bos et al., 1993; Humphrey et al., 1993; Wong and Hong, 1993) . This motif has also been shown to be sufficient for localizing heterologous proteins, such as the LDL receptor and the Tac antigen (interleukin-2 receptor A-chain) to the TGN (Bos et al., 1993; Humphrey et al., 1993) . A mutant version of the sis-TGN38 construct, referred to as sis-TGN38A, was constructed using only the 28 amino acids of TGN38 that encompass the transmembrane domain. Thus, the sis-TGN38A construct lacks the essential tyrosine-containing motif, and should not be retained in the TGN.