Ligation of the B cell antigen receptor (BCR) complex initiates tyrosine phosphorylation of the receptor's transducer components, Ig-α and Ig-β and tyrosine kinase-dependent accumulation of GTP-bound, activated p21(ras). The mechanism of receptor coupling to p21(ras) activation and the roles of Ig-α and Ig-β are unknown. The results reported here indicate that the resting, non-phosphorylated BCR associates with the Grb-2/Sos-linker SHC via the Ig-α immunoreceptor-based tyrosine activation motif (ITAM). Ig-α specificity of this interaction is determined by the sequence DCSM found in Ig-α, but not Ig-β. Tyrosine phosphorylation of Ig-α and Ig-β ITAM allows recruitment of SHC, which now binds directly to both Ig-α and Ig-β via a phosphotyrosine/SH2 interaction. In confirmation of recent studies by Saxton et al. receptor ligation leads to tyrosine phosphorylation of SHC and to the formation of a phospho-SHC/Grb2/Sos complex. In view of previous studies which demonstrated p21(ras) co-capping with ligated BCR, the data presented here suggest that Ig-α/β- and SHC tyrosine phosphorylation-dependent recruitment of the Grb2/Sos complex to the receptor can occur and may provide a mechanism by which the nucleotide exchange activity of Sos could mediate activation of BCR-localized p21(ras).
- B cell receptor signaling