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PMID: 10993915 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 192 ·No. 6 ·2000-09-18 ·Pages 847-56

Ishiai M, Kurosaki M, Inabe K, Chan AC, Sugamura K, Kurosaki T

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals B-Lymphocytes/immunology Carrier Proteins/immunology,metabolism Cell Membrane/immunology Chickens ErbB Receptors/physiology GRB2 Adaptor Protein Gene Library Humans Membrane Proteins Phosphoproteins/immunology,metabolism Proteins/metabolism Receptors, Antigen, B-Cell/immunology Receptors, Antigen, T-Cell/immunology Recombinant Proteins/immunology,metabolism Signal Transduction
Chemicals
Adaptor Proteins, Signal Transducing B cell linker protein Carrier Proteins GRAP2 protein, human GRB2 Adaptor Protein GRB2 protein, human LAT protein, human Membrane Proteins Phosphoproteins Proteins Receptors, Antigen, B-Cell Receptors, Antigen, T-Cell Recombinant Proteins SLP-76 signal Transducing adaptor proteins ErbB Receptors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ishiai M
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan.
Kurosaki M
Inabe K
Chan A C
Sugamura K
Kurosaki T
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.192.6.847
Published
2000-09-18
Pages
847-56
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193288
Subset
IM
Grants
NIAID NIH HHS · R01AI42787 · United States
External Links
PubMed source DOI: 10.1084/jem.192.6.847 PMC Full Text View journal details
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