CARBOXYL-TERMINAL TARGETING AND NOVEL POSTTRANSLATIONAL PROCESSING OFJAW1, A LYMPHOID PROTEIN OF THE ENDOPLASMIC-RETICULUM

Jaw1 is a lymphoid-restricted protein localized to the cytoplasmic fac e of the endoplasmic reticulum (ER) and is a member of a recently reco gnized class of integral membrane proteins that contain carboxyl-termi nal membrane anchors. The carboxyl-terminal 71 amino acids of the Jaw1 protein, which contain a hydrophobic membrane spanning region, are su fficient to target a heterologous protein to the ER. By discontinuous sucrose gradient ultracentrifugation, differential sedimentation was n oted for the four major Jaw1 protein isoforms, with two of the forms p redominantly soluble and two microsome-bound. Pulse-chase immunoprecip itations suggest a post translational modification of two major isofor ms of the protein resulting in an increase in mobility on SDS-polyacry lamide gel electrophoresis. In. vitro translation studies are compatib le with a posttranslational processing event that results in cleavage of a short 36 amino acid lumenal domain. These findings define a carbo xyl-terminal domain of the Jaw1 protein that is both necessary and suf ficient for ER localization. In addition, the processing of the small lumenal domain of Jaw1 represents a novel post-translational protein m odification performed by the endoplasmic reticulum.