酪氨酸磷酸化通过调节CTLA-4与网格蛋白相关衔接复合物AP-2的相互作用来控制CTLA-4的内化。

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

作者信息

Shiratori T, Miyatake S, Ohno H, Nakaseko C, Isono K, Bonifacino J S, Saito T

机构信息

Division of Molecular Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chuo-ku, Japan.

出版信息

Immunity. 1997 May;6(5):583-9. doi: 10.1016/s1074-7613(00)80346-5.

DOI:10.1016/s1074-7613(00)80346-5

PMID:9175836

Abstract

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 mu2 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 mu2 requires unphosphorylated tyrosine. The interaction with mu2 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.

摘要

CTLA-4是一种共刺激受体，它以高亲和力与CD28结合相同的配体CD80和CD86，并在活化T细胞的细胞表面短暂表达。CTLA-4通过其胞质结构域中含磷酸酪氨酸的基序与Syp酪氨酸磷酸酶结合来传递抑制信号。我们现在证明，CTLA-4通过与Syp相互作用所涉及的相同基序与质膜相关衔接复合体AP-2的μ2亚基相互作用，只是与μ2的相互作用需要未磷酸化的酪氨酸。与μ2的相互作用可能诱导CTLA-4从细胞表面快速内化。我们的结果表明，单个酪氨酸残基的磷酸化状态决定了CTLA-4是传递负信号还是被内化。