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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane.

B cell linker protein ( BLNK) and Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76) are adaptor proteins required for B cell receptor (BCR) and T cell receptor function, respectively. Here, we show that expression of SLP-76 cannot reconstitute BCR function in Zap-70(+)BLNK(-) B cells. This could be attributable to inability of SLP-76 to be recruited into glycolipid-enriched microdomains (GEMs) after antigen receptor cross-linking. Supporting this idea, the BCR function was restored when a membrane-associated SLP-76 chimera was enforcedly localized to GEMs. Moreover, we demonstrate that addition of both linker for activation of T cells (LAT) and Grb2-related adaptor downstream of Shc (Gads) to SLP-76 allow SLP-76 to be recruited into GEMs, whereby the BCR function is reconstituted. The Gads function was able to be replaced by overexpression of Grb2. In contrast to SLP-76, BLNK did not require Grb2 families for its recruitment to GEMs. Hence, these data suggest a functional overlap between BLNK and SLP-76, while emphasizing the difference in requirement for additional adaptor molecules in their targeting to GEMs.[1]


  1. Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane. Ishiai, M., Kurosaki, M., Inabe, K., Chan, A.C., Sugamura, K., Kurosaki, T. J. Exp. Med. (2000) [Pubmed]
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