Hutchings Nicholas J, Clarkson Nicholas, Chalkley Robert, Barclay A Neil, Brown Marion H
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom.
J Biol Chem. 2003 Jun 20;278(25):22396-403. doi: 10.1074/jbc.M302540200. Epub 2003 Apr 10.
Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322-339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322-339 with similar dissociation constants (KD = approximately 100 microm). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C-terminal half or the N-terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ.
抗原刺激下，CD2募集至免疫突触依赖于其富含脯氨酸的胞质尾。从该区域分离出的一段肽（CD2:322 - 339）可结合CMS（人CD2相关蛋白）、一种相关蛋白CIN85以及来自T细胞系的肌动蛋白封端蛋白CAPZ。在BIAcore分析中，CMS和CIN85的N端SH3结构域以相似的解离常数（KD约为100微摩尔）结合CD2:322 - 339。CAPZ结合CMS和CIN85的C端一半区域。CMS/CIN85与CAPZ之间的直接结合建立了与肌动蛋白细胞骨架的联系。在小鼠T细胞杂交瘤中过表达CD2AP C端一半区域或N端SH3结构域的片段，可导致抗原刺激下白细胞介素-2产生增加以及T细胞受体下调减少。这些衔接蛋白在T细胞信号传导中很重要，这与CD2在调节由CMS/CIN85和CAPZ启动的信号通路中的作用一致。
