Characterization of Posttranslational Modifications of Human A33 Antigen, a Novel Palmitoylated Surface Glycoprotein of Human Gastrointestinal Epithelium Academic Article uri icon

abstract

  • Monoclonal antibody (mAb) A33 recognizes a differentiation antigen (A33) expressed in normal human gastrointestinal epithelium and in 95% of human colon cancers. Murine mAb A33 shows specific targeting of colon cancer in humans and a humanized A33 antibody is currently being evaluated in the clinic. The cDNA for the human A33 antigen has recently been cloned, and sequence comparison indicated that the A33 antigen is a novel human cell surface molecule of the immunoglobulin superfamily. Because mAb A33 recognizes a conformational epitope, only a partial characterization of the A33 antigen has been carried out to date. In this report we show that the A33 antigen is (I) N-glycosylated, containing approximately 8 K of N-linked carbohydrate and there is no evidence for O-glycosylation, sialylation or glycophosphatidylinositol, and (ii) S-acylated in vitro, incorporating [3H] palmitic acid linked through a hydroxylamine-sensitive thioester bond. The S-palmitoylation may be involved in regulating the internalization process initiated by binding of mAb A33 to cell surface A33 antigen.

authors

  • Ritter, Gerd
  • Cohen, Leonard S
  • Nice, Edouard C
  • Catimel, Bruno
  • Burgess, Antony W
  • Moritz, Robert L
  • Ji, Hong
  • Heath, Joan K
  • White, Sara J
  • Welt, Sydney
  • Old, Lloyd J
  • Simpson, Richard J

publication date

  • July 1997