Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads.

ABSTRACT: The transmembrane protein, linker for activation of T cells (LAT), is essential for T-cell activation and development. Phosphorylation of LAT at multiple tyrosines creates binding sites for the adaptors Gads and Grb2, leading to nucleation of multiprotein signaling complexes. Human LAT contains five potential binding sites for Gads, of which only those at Tyr171 and Tyr191 appear necessary for T-cell function. We asked whether Gads binds preferentially to these sites, as differential recognition could assist in assembling defined LAT-based complexes. Measured calorimetrically, Gads-SH2 binds LAT tyrosine phosphorylation sites 171 and 191 with higher affinities than the other sites, with the differences ranging from only several fold weaker binding to no detectable interaction. Crystal stru

SUBMITTER: Cho S 

PROVIDER: S-EPMC391073 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature