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

被引:35
|
作者
DAmbrosio, D
Hippen, KL
Cambier, JC
机构
[1] NATL JEWISH CTR IMMUNOL & RESP MED,DEPT PEDIAT,DIV BASIC SCI,DENVER,CO 80206
[2] UNIV COLORADO,HLTH SCI CTR,DEPT MICROBIOL & IMMUNOL,DENVER,CO 80262
关键词
Ig-alpha; SHC; B cell receptor signaling;
D O I
10.1002/eji.1830260842
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ligation of the B cell antigen receptor (BCR) complex initiates tyrosine phosphorylation of the receptor's transducer components, Ig-alpha and Ig-beta 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-alpha and Ig-beta are unknown. The results reported here indicate that the resting, nonphosphorylated BCR associates with the Grb-2/Sos-linker SHC via the Ig-alpha immunoreceptor-based tyrosine activation motif (ITAM). Ig-alpha specificity of this interaction is determined by the sequence DCSM found in Ig-alpha, but not Ig-beta. Tyrosine phosphorylation of Ig-alpha and Ig-beta ITAM allows recruitment of SHC, which now binds directly to both Ig-alpha and Ig-beta 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 p21(ras) co-capping with ligated BCR, the data presented here suggest that Ig-alpha/beta- ard 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).
引用
收藏
页码:1960 / 1965
页数:6
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