Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
J Immunol. 2009 Dec 15;183(12):7966-74. doi: 10.4049/jimmunol.0902096.
Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2-like domains, as well as a YXXQ motif in its C-terminal region. Our previous studies revealed that STAP-2 regulates integrin-mediated T cell adhesion. In the present study, we find that STAP-2 expression affects Jurkat T cell migration after stromal cell-derived factor-1alpha (SDF-1alpha)-treatment. Furthermore, STAP-2-deficient T cells exhibit reduced cell migration after SDF-1alpha-treatment. Importantly, overexpression of STAP-2 in Jurkat T cells induces activation of small guanine triphosphatases, such as Rac1 and Cdc42. Regarding the mechanism for this effect, we found that STAP-2 associates with Vav1, the guanine-nucleotide exchanging factor for Rac1, and enhances downstream Vav1/Rac1 signaling. These results reveal a novel STAP-2-mediated mechanism for the regulation of SDF-1alpha-induced chemotaxis of T cells via activation of Vav1/Rac1 signaling.
信号转导衔接蛋白-2（STAP-2）是一种新鉴定的衔接蛋白，其包含pleckstrin 和Src 同源 2 样结构域，以及其 C 末端区域的一个 YXXQ 基序。我们先前的研究表明，STAP-2 调节整合素介导的 T 细胞黏附。在本研究中，我们发现 STAP-2 表达影响基质细胞衍生因子-1α（SDF-1α）处理后的 Jurkat T 细胞迁移。此外，STAP-2 缺陷型 T 细胞在 SDF-1α处理后迁移减少。重要的是，在 Jurkat T 细胞中转染过表达 STAP-2 可诱导小 GTP 酶的激活，如 Rac1 和 Cdc42。关于这种效应的机制，我们发现 STAP-2 与 Rac1 的鸟嘌呤核苷酸交换因子 Vav1 相关，并增强下游 Vav1/Rac1 信号。这些结果揭示了一种新的 STAP-2 介导的机制，通过激活 Vav1/Rac1 信号来调节 SDF-1α诱导的 T 细胞趋化性。
