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....

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Main Authors:	Ishiai, Masamichi, Kurosaki, Mari, Inabe, Kazunori, Chan, Andrew C., Sugamura, Kazuo, Kurosaki, Tomohiro
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2000
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193288/

id	pubmed-2193288
recordtype	oai_dc
spelling	pubmed-21932882008-04-16 Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane Ishiai, Masamichi Kurosaki, Mari Inabe, Kazunori Chan, Andrew C. Sugamura, Kazuo Kurosaki, Tomohiro Original Article 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. The Rockefeller University Press 2000-09-18 /pmc/articles/PMC2193288/ /pubmed/10993915 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ishiai, Masamichi Kurosaki, Mari Inabe, Kazunori Chan, Andrew C. Sugamura, Kazuo Kurosaki, Tomohiro
spellingShingle	Ishiai, Masamichi Kurosaki, Mari Inabe, Kazunori Chan, Andrew C. Sugamura, Kazuo Kurosaki, Tomohiro Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
author_facet	Ishiai, Masamichi Kurosaki, Mari Inabe, Kazunori Chan, Andrew C. Sugamura, Kazuo Kurosaki, Tomohiro
author_sort	Ishiai, Masamichi
title	Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
title_short	Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
title_full	Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
title_fullStr	Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
title_full_unstemmed	Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
title_sort	involvement of lat, gads, and grb2 in compartmentation of slp-76 to the plasma membrane
description	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.
publisher	The Rockefeller University Press
publishDate	2000
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193288/
_version_	1611431002754777088

Involvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane

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