Distinct mechanisms mediate SHC association with the activated and resting B cell antigen receptor

Publisher Website
Google Scholar
Abstract
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 p21ras. The mechanism of receptor coupling to p21ras activation and the roles of Ig‐α and Ig‐β are unknown. The results reported here indicate that the resting, nonphosphorylated 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. (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 p21ras 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 p21ras.