Premium
Mutational suppression of transferrin receptor shedding can be compensated by distinct metalloproteases acting on alternative sites
Author(s) -
Dassler Katrin,
Kaup Matthias,
Tauber Rudolf,
Fuchs Hendrik
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00004-8
Subject(s) - ectodomain , transferrin receptor , metalloproteinase , cleavage (geology) , receptor , biology , transferrin , furin , transfection , microbiology and biotechnology , gene , biochemistry , matrix metalloproteinase , enzyme , paleontology , fracture (geology)
The human transferrin receptor (TfR) is proteolytically cleaved at R100 within the juxtamembrane stalk and to a lesser extent at an alternative site. We examined the effect of stalk mutations on human TfR shedding in transfected CHO cells. Point mutations at R100 led to an increase in alternative shedding while the R100 cleavage product was undetectable. Replacing the TfR‐stalk by the corresponding sequences from tumor necrosis factor‐α or interleukin‐6 receptor also led to TfR ectodomain shedding. These results show that cleavage at alternative sites can compensate for suppressed cleavage at the major site and inhibitor studies reveal that at least three metalloproteases are involved in the shedding process.