Distinct mechanisms mediate SHC association with the activated and resting B cell antigen receptor
Ligation of the B cell antigen receptor (BCR) complex initiates tyrosine phosphorylation of the receptor's transducer components, Ig-a and Ig-p and tyrosine kinase-dependent accumulation of GTP-bound, activated ~2 1 ~' .
The mechanism of receptor coupling to ~2 1 " ~ activation and the roles of Ig-a and Ig-f3 are unknown. The results reported here indicate that the resting, nonphosphorylated BCR associates with the Grb-21Sos-linker SHC via the Ig-a immunoreceptor-based tyrosine activation motif (ITAM). Ig-a specificity of this interaction is determined by the sequence DCSM found in Ig-a, but not Ig-p. Tyrosine phosphorylation of Ig-a and Ig-p ITAM allows recruitment of SHC, which now binds directly to both Ig-a and Ig-f3 via a phosphotyrosine/SH2 interaction. In confirmation of recent studies by Saxton et al. ( J . Immunol. 1994.153: 623) 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 ~2 1 ' " ~ co-capping with ligated BCR, the data presented here suggest that Ig-a/p-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 ~21'"'.