Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis

被引：301

作者：

Motyka, B

Korbutt, G

Pinkoski, MJ

Heibein, JA

Caputo, A

Hobman, M

Barry, M

Shostak, I

Sawchuk, T

Holmes, CFB

Gauldie, J

Bleackley, RC ^{[1
]}

机构：

[1] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada

[2] Univ Alberta, Dept Surg, Edmonton, AB T6G 2H7, Canada

[3] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

来源：

CELL | 2000年 / 103卷 / 03期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/S0092-8674(00)00140-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The serine proteinase granzyme B is crucial for the rapid induction of target cell apoptosis by cytotoxic T cells. Granzyme B was recently demonstrated to enter cells in a perforin-independent manner, thus predicting the existence of a cell surface receptor(s). We now present evidence that this receptor is the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR). Inhibition of the granzyme B-CI-MPR interaction prevented granzyme B cell surface binding, uptake, and the induction of apoptosis. Significantly, expression of the CI-MPR was essential for cytotoxic T cell-mediated apoptosis of target cells in vitro and for the rejection of allogeneic cells in vivo. These results suggest a novel target for immunotherapy and a potential mechanism used by tumors for immune evasion.

引用

页码：491 / 500

页数：10

共 66 条

[1] Comparison of the human versus murine cytomegalovirus immediate early gene promoters for transgene expression by adenoviral vectors [J].