Lad, a T-cell specific adaptor protein, mediates the chemokine signaling through association with G_(β) in T cells

다국어 초록 (Multilingual Abstract)

To identify the functions of Lad in T cell activation, Yeast two-hybrid screening was performed with Lad as bait. Characterization of positives revealed that Lad interacted with G-protein β subunits known as a mediator of chemokine-dependent signaling. The Lad-G_(β)1 interaction was confirmed in coimmunoprecipitation studies in Cos-7 cells. Furthermore, in Jurkat T-cell lines stably expressing Lad, the binding of Lad to G_(β) subunit was significantly induced in response to RANTES or SDF-1α treatment but not to CD3 activation. Importantly, the tyrosine phosphorylation of Lad and the interaction of Lad with p56^(Lck) were increased upon RANTES or SDF-1α treatment. Upon treatment with RANTES or SDF-1α, the phosphorylation level of p42/44 MAPK was 2-3 fold higher in Lad-overexpressing stable cells compared to control cells, whereas the phosphorylation of MAPK was impaired in Lad-SH2(dominant negative form)-expressing stable cells. These results suggest that Lad mediates chemokine signaling through association with G_(β) and possibly plays an important role in migration and homing.