Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2

被引:289
作者
Shiratori, T
Miyatake, S
Ohno, H
Nakaseko, C
Isono, K
Bonifacino, JS
Saito, T
机构
[1] CHIBA UNIV,SCH MED,CTR BIOMED SCI,DIV MOL GENET,CHUO KU,CHIBA 280,JAPAN
[2] CHIBA UNIV,SCH MED,DEPT SURG 2,CHUO KU,CHIBA 280,JAPAN
[3] NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892
关键词
D O I
10.1016/S1074-7613(00)80346-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CTLA-4 is a costimulation receptor that binds to the same ligands, CD80 and CD86, as CD28 with high affinity and is transiently expressed on the cell surface of activated T cells. CTLA-4 delivers an inhibitory signal through association of a phosphotyrosine-containing motif in the cytoplasmic domain with Syp tyrosine phosphatase. We now demonstrate that CTLA-4 interacts with the mu(2) subunit of the plasma membrane-associated adaptor complex, AP-2, through the same motif involved in the interaction with Syp, except that the interaction with mu(2) requires unphosphorylated tyrosine. The interaction with mu(2) likely induces rapid internalization of CTLA-4 from the cell surface. Our results suggest that the phosphorylation state of a single tyrosine residue determines whether CTLA-4 delivers a negative signal or is internalized.
引用
收藏
页码:583 / 589
页数:7
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