Mutational suppression of transferrin receptor shedding can be compensated by distinct metalloproteases acting on alternative sites

FEBS Letters

Dassler, Katrin¹  Kaup, Matthias¹  Tauber, Rudolf¹  Fuchs, Hendrik¹ 

[1] Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany

关键词: Ectodomain shedding;    Metalloprotease;    Serum transferrin receptor;    Interleukin-6 receptor;    Tumor necrosis factor-α;    ADAM;    ADAM;    a disintegrin and metalloproteinase;    FCI;    furin convertase inhibitor;    IL-6R;    interleukin-6 receptor;    MMP;    matrix metalloproteinase;    sTfR;    soluble TfR;    TAPI;    TNF-α protease inhibitor;    TNF-α;    tumor necrosis factor-α;    TfR;    transferrin receptor;    TIMP;    tissue inhibitor of metalloproteinases;    wt-TfR;    wild-type transferrin receptor;   

DOI  :  10.1016/S0014-5793(03)00004-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown