Lipid rafts: cell surface platforms for T cell signaling

The Src family tyrosine kinase Lck is essential for T cell development and T cell receptor (TCR)* signaling. Lck is post-translationally fatty acylated at its N-terminus conferring membrane targeting and concentration in plasma membrane lipid rafts, which are lipid-based organisational platforms. Co...

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Autores principales:	MAGEE,TONY, PIRINEN,NIINA, ADLER,JEREMY, PAGAKIS,STAMATIS N, PARMRYD,INGELA
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2002
Materias:	lipid rafts Lck tyrosine kinase T cell signalling phosphatase
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200003
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spelling	oai:scielo:S0716-976020020002000032002-12-26Lipid rafts: cell surface platforms for T cell signalingMAGEE,TONYPIRINEN,NIINAADLER,JEREMYPAGAKIS,STAMATIS NPARMRYD,INGELA lipid rafts Lck tyrosine kinase T cell signalling phosphatase The Src family tyrosine kinase Lck is essential for T cell development and T cell receptor (TCR)* signaling. Lck is post-translationally fatty acylated at its N-terminus conferring membrane targeting and concentration in plasma membrane lipid rafts, which are lipid-based organisational platforms. Confocal fluorescence microscopy shows that Lck colocalises in rafts with GPI-linked proteins, the adaptor protein LAT and Ras, but not with non-raft membrane proteins including the protein tyrosine phosphatase CD45. The TCR also associates with lipid rafts and its cross-linking causes coaggregation of raft-associated proteins including Lck, but not of CD45. Cross-linking of either the TCR or rafts strongly induces specific tyrosine phosphorylation of the TCR in the rafts. Remarkably, raft patching alone induces signalling events analogous to TCR stimulation, with the same dependence on expression of key TCR signalling molecules. Our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts, which facilitates colocalisation of signaling proteins including Lck, LAT, and the TCR, while excluding CD45, thereby potentiating protein tyrosine phosphorylation and downstream signaling. We are currently testing this hypothesis as well as using imaging techniques such as fluorescence resonance energy transfer (FRET) microscopy to study the dynamics of proteins and lipids in lipid rafts in living cells undergoing signaling events. Recent data show that the key phosphoinositide PI(4,5)P2 is concentrated in T cell lipid rafts and that on stimulation of the cells it is rapidly converted to PI(3,4,5)P3 and diacylglycerol within rafts. Thus rafts are hotspots for both protein and lipid signalling pathways.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.35 n.2 20022002-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200003en10.4067/S0716-97602002000200003
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	lipid rafts Lck tyrosine kinase T cell signalling phosphatase
spellingShingle	lipid rafts Lck tyrosine kinase T cell signalling phosphatase MAGEE,TONY PIRINEN,NIINA ADLER,JEREMY PAGAKIS,STAMATIS N PARMRYD,INGELA Lipid rafts: cell surface platforms for T cell signaling
description	The Src family tyrosine kinase Lck is essential for T cell development and T cell receptor (TCR)* signaling. Lck is post-translationally fatty acylated at its N-terminus conferring membrane targeting and concentration in plasma membrane lipid rafts, which are lipid-based organisational platforms. Confocal fluorescence microscopy shows that Lck colocalises in rafts with GPI-linked proteins, the adaptor protein LAT and Ras, but not with non-raft membrane proteins including the protein tyrosine phosphatase CD45. The TCR also associates with lipid rafts and its cross-linking causes coaggregation of raft-associated proteins including Lck, but not of CD45. Cross-linking of either the TCR or rafts strongly induces specific tyrosine phosphorylation of the TCR in the rafts. Remarkably, raft patching alone induces signalling events analogous to TCR stimulation, with the same dependence on expression of key TCR signalling molecules. Our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts, which facilitates colocalisation of signaling proteins including Lck, LAT, and the TCR, while excluding CD45, thereby potentiating protein tyrosine phosphorylation and downstream signaling. We are currently testing this hypothesis as well as using imaging techniques such as fluorescence resonance energy transfer (FRET) microscopy to study the dynamics of proteins and lipids in lipid rafts in living cells undergoing signaling events. Recent data show that the key phosphoinositide PI(4,5)P2 is concentrated in T cell lipid rafts and that on stimulation of the cells it is rapidly converted to PI(3,4,5)P3 and diacylglycerol within rafts. Thus rafts are hotspots for both protein and lipid signalling pathways.
author	MAGEE,TONY PIRINEN,NIINA ADLER,JEREMY PAGAKIS,STAMATIS N PARMRYD,INGELA
author_facet	MAGEE,TONY PIRINEN,NIINA ADLER,JEREMY PAGAKIS,STAMATIS N PARMRYD,INGELA
author_sort	MAGEE,TONY
title	Lipid rafts: cell surface platforms for T cell signaling
title_short	Lipid rafts: cell surface platforms for T cell signaling
title_full	Lipid rafts: cell surface platforms for T cell signaling
title_fullStr	Lipid rafts: cell surface platforms for T cell signaling
title_full_unstemmed	Lipid rafts: cell surface platforms for T cell signaling
title_sort	lipid rafts: cell surface platforms for t cell signaling
publisher	Sociedad de Biología de Chile
publishDate	2002
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200003
work_keys_str_mv	AT mageetony lipidraftscellsurfaceplatformsfortcellsignaling AT pirinenniina lipidraftscellsurfaceplatformsfortcellsignaling AT adlerjeremy lipidraftscellsurfaceplatformsfortcellsignaling AT pagakisstamatisn lipidraftscellsurfaceplatformsfortcellsignaling AT parmrydingela lipidraftscellsurfaceplatformsfortcellsignaling
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Lipid rafts: cell surface platforms for T cell signaling

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