TUMOR-SPECIFIC CELL-SURFACE EXPRESSION OF THE -KDEL CONTAINING, ENDOPLASMIC RETICULAR HEAT-SHOCK PROTEIN GP96

Heat shock protein (HSP) gp96/grp94 contains a signal peptide at the a mino terminus and a -KDEL sequence at the carboxy terminus and is a ma jor component of the lumen of the mammalian endoplasmic reticulum (ER) , We show, by a number of immunolocalization methods using light and e lectron microscopy, that a significant proportion of intact gp96 molec ules is also expressed on the cell surface, Surface gp96 molecules tru ly represent surface expression and do not result from adventitious de position of gp96 released by dead cells on to the live cells in cultur e. Cell surface expression of gp96 is enhanced by heat shock and expos ure to reducing agents, Gp96 molecules are not released from plasma me mbranes by repeated salt washes, and gp96 is not an integral membrane protein, Our observations suggest that gp96 and perhaps other HSPs are anchored to the cell surface as part of larger molecular complexes, w hich also transport them to the cell surface. (C) 1996 Wiley-Liss, Inc .