threonine kinase sgk-1 (original) (raw)

System L is the major Na¤-independent amino acid transporter of mammalian cells (Christensen, 1990). It is constituted of the type II membrane protein 4F2hc (CD98) which is covalently linked to the polytopic membrane protein LAT1 via a disulfide bridge (Br oer et al. 1995, 1997a; Mastroberardino et al. 1998; Kanai et al. 1998). The transport pore of the transporter is most probably constituted by LAT1 (Pfeiffer et al. 1998), whereas 4F2hc is necessary for the translocation of the complex into the plasma membrane (Mastroberardino et al. 1998; Kanai et al. 1998; Nakamura et al. 1999). Western blotting and immunofluorescence studies show that 4F2hc is located in the plasma membrane in the absence of LAT1, whereas LAT1, when expressed alone, does not reach the surface of the oocyte (Mastroberardino et al. 1998; Kanai et al. 1998; Nakamura et al. 1999). The role of the 4F2hc protein in plasma membrane trafficking is further supported by its interaction with a family of amino acid transporters. In the absence of LAT1, expression in oocytes of 4F2hc alone results in the plasma membrane insertion of a number of endogenous amino acid transporters, e.g. the 2-amino-[2,2,1]heptane-2-carboxylic acid (BCH)-inhibitable system b 0,+ , system y¤L and some as yet unidentified transporters (Chillaron et al. 1996; Br oer et al. 1998a; Estevez et al. 1998). Subsequent to the cloning of the LAT1 cDNA, additional light chains have been identified which also interact with the 4F2hc protein to form other amino acid transporters with different substrate specificities, namely LAT2, y¤LAT1, y¤LAT2 and xCT (Torrents et al. 1998;