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Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor

A receptor surface Ig (sIg) signaling variant of WEHI-231 was constructed to investigate components and linkages between various signaling events associated with signal transduction through sIg. Unlike the wildtype, crosslinking of sIgM on VS2.12-cl.2 did not result in downregulation of proliferatio...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1989
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189292/
https://www.ncbi.nlm.nih.gov/pubmed/2494290
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description A receptor surface Ig (sIg) signaling variant of WEHI-231 was constructed to investigate components and linkages between various signaling events associated with signal transduction through sIg. Unlike the wildtype, crosslinking of sIgM on VS2.12-cl.2 did not result in downregulation of proliferation. Similarly, receptor crosslinking was uncoupled from inositol phospholipid (PI) hydrolysis and upregulation of c-fos expression in the variant. The signaling defect in VS2.12-cl.2 appears to be proximal to phospholipase C activation as direct G protein activation by A1F4- triggers PI hydrolysis and bypassing PI hydrolysis using phorbol diester stimulation of protein kinase C restores the inhibitable phenotype and the ability to upregulate c-fos. Even more interesting, sIg-linked Ca2+ responses by VS2.12-cl.2 are equivalent to these observed in the wildtype WEHI-231. These latter results suggest that contrary to current thought, sIg- generated signals may not be coupled to Ca2+ fluxes entirely via inositol phospholipid hydrolysis. Thus, VS2.12-cl.2 is a new and powerful tool with which to analyze signaling through sIg at the molecular level.
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spelling pubmed-21892922008-04-17 Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor J Exp Med Articles A receptor surface Ig (sIg) signaling variant of WEHI-231 was constructed to investigate components and linkages between various signaling events associated with signal transduction through sIg. Unlike the wildtype, crosslinking of sIgM on VS2.12-cl.2 did not result in downregulation of proliferation. Similarly, receptor crosslinking was uncoupled from inositol phospholipid (PI) hydrolysis and upregulation of c-fos expression in the variant. The signaling defect in VS2.12-cl.2 appears to be proximal to phospholipase C activation as direct G protein activation by A1F4- triggers PI hydrolysis and bypassing PI hydrolysis using phorbol diester stimulation of protein kinase C restores the inhibitable phenotype and the ability to upregulate c-fos. Even more interesting, sIg-linked Ca2+ responses by VS2.12-cl.2 are equivalent to these observed in the wildtype WEHI-231. These latter results suggest that contrary to current thought, sIg- generated signals may not be coupled to Ca2+ fluxes entirely via inositol phospholipid hydrolysis. Thus, VS2.12-cl.2 is a new and powerful tool with which to analyze signaling through sIg at the molecular level. The Rockefeller University Press 1989-03-01 /pmc/articles/PMC2189292/ /pubmed/2494290 Text en 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/).
spellingShingle Articles
Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor
title Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor
title_full Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor
title_fullStr Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor
title_full_unstemmed Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor
title_short Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor
title_sort isolation and characterization of a b lymphocyte mutant with altered signal transduction through its antigen receptor
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189292/
https://www.ncbi.nlm.nih.gov/pubmed/2494290