Recruitment of GADS:SLP-76 to p-5Y-LAT

Gads/GRAP2 (GRB2-related adapter protein 2) is member of the GRB2 adaptor family with a central SH2 domain and linker region flanked by amino- and carboxy-terminal SH3 domains. SLP-76 associates constitutively via its central 20-amino acid proline-rich domain with the C-terminal SH3 domain of Gads, which recruits it to LAT following receptor stimulation. Upon LAT phosphorylation, Gads:SLP-76 complex principally binds to phosphorylated LAT tyrosine 191, with a reduced amount of binding to phosphorylated tyrosine 171 and no interaction with phosphorylated tyrosines 132 or 226 (Houtman et al. 2004, Zhu et al. 2003). Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways (Liu et al. 1999). The LAT-Gads-SLP-76 complex creates a platform for the recruitment of multiple signaling molecules, including PLCgamma1, GRB2, NCK, Rho GEFs, VAV and the Tec-family kinases ITK and BTK (Liu et al. 1999 & 2001, Asada et al. 1999, Yablonski et al. 2001).

Gads/GRAP2（GRB2相关适配蛋白2）属于GRB2适配蛋白家族，其核心区域包含SH2结构域和连接区域，两侧分别被氨基末端和羧基末端的SH3结构域所包围。SLP-76通过其核心的富含脯氨酸的20个氨基酸结构域，以构成性方式与Gads的羧基末端SH3结构域相结合，从而在受体刺激后将其募集到LAT。在LAT磷酸化后，Gads:SLP-76复合物主要与磷酸化的LAT酪氨酸191结合，结合量有所减少的是磷酸化的酪氨酸171，并且与磷酸化的酪氨酸132或226无相互作用（Houtman等人，2004，Zhu等人，2003）。Gads可能促进LAT和SLP-76信号复合物之间的串扰，从而将膜近端事件耦合至下游信号通路（Liu等人，1999）。LAT-Gads-SLP-76复合物为多种信号分子的募集提供了一个平台，包括PLCgamma1、GRB2、NCK、Rho GEFs、VAV以及Tec家族激酶ITK和BTK（Liu等人，1999 & 2001，Asada等人，1999，Yablonski等人，2001）。