Further evidence for a common mechanism for shedding of cell surface proteins

• Published in: FEBS letters Vol. 401; no. 2; pp. 235 - 238
• Main Authors: Müllberg, Jürgen, Rauch, Charles T, Wolfson, Martin F, Castner, Beverly, Fitzner, Jeffrey N, Otten-Evans, Carol, Mohler, Kendall M, Cosman, David, Black, Roy A
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 20.01.1997
• Subjects: Animals; Cell Line; COS Cells; Dipeptides - pharmacology; Humans; Hydroxamic Acids - pharmacology; Limited proteolysis; Membrane Proteins - metabolism; Metalloprotease; Protease inhibitor; Receptors, Interleukin - metabolism; Shedding; soluble form of the p80 TNFR linked to the constant region of the human Ig heavy chain; Stem Cell Factor - metabolism; TNFR-Fc; Tumor Necrosis Factor-alpha - metabolism; Metalloprotease; Shedding; TNFR-Fc; Limited proteolysis; Protease inhibitor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(96)01480-9

Pro-TNFα, Steel factor, type II IL-1R and IL-2Rα were expressed in COS-7 cells and the generation of their soluble forms was examined. The release of all four proteins was strongly stimulated by the phorbol ester PMA and completely blocked by a hydroxamate-based inhibitor of metalloproteases. COS-7 cell membranes were found to cleave various synthetic pro-TNFα peptides with the same specificity as a partially purified TNFα converting enzyme purified from human monocytic cells, suggesting that the same enzyme may be responsible for at least some of the COS-7 cell shedding activity.