Further evidence for a common mechanism for shedding of cell surface proteins.
Pro-TNF alpha, Steel factor, type II IL-1R and IL-2R alpha 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-TNF alpha peptides with the same specificity as a partially purified TNF alpha 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.
Müllberg
J
J
Immunex Corporation, Seattle, WA 98101, USA. mullbergj@immunex.com
Rauch
C T
CT
Wolfson
M F
MF
Castner
B
B
Fitzner
J N
JN
Otten-Evans
C
C
Mohler
K M
KM
Cosman
D
D
Black
R A
RA
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004151:Dipeptides; D006877:Hydroxamic Acids; D008565:Membrane Proteins; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D018123:Receptors, Interleukin; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha