Regulation of T‐cell receptor signalling by membrane microdomains

Razzaq, Tahir M.; Ozegbe, Patricia; Jury, Elizabeth C.; Sembi, Phupinder; Blackwell, Nathan M.; Kabouridis, Panagiotis S.

doi:10.1111/j.1365-2567.2004.01998.x

Cited by 86 publications

(77 citation statements)

References 186 publications

(346 reference statements)

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“…Lipid rafts are dynamic assemblies floating freely in the surrounding membranes of living cells. The proteins participating in lipid rafts in T lymphocytes have been studied with proteomics [154][155][156][157][158], and the subject was recently reviewed by Wollscheid et al [159] and by Razzaq et al [160]. MS was used by Li et al [158] to specifically detect proteins depleted from rafts by cholesterol-disrupting drugs.…”

Section: Leukocytesmentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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Service régional vaudois de transfusion sanguine, Lausanne, SwitzerlandBlood is divided in two compartments, namely, plasma and cells. The latter contain red blood cells, leukocytes, and platelets. From a descriptive medical discipline, hematology has evolved towards a pioneering discipline where molecular biology has permitted the development of prognostic and diagnostic indicators for disease. The recent advance in MS and protein separation now allows similar progress in the analysis of proteins. Proteomics offers great promise for the study of proteins in plasma/serum, indeed a number of proteomics databases for plasma/ serum have been established. This is a very complex body fluid containing lipids, carbohydrates, amino acids, vitamins, nucleic acids, hormones, and proteins. About 1500 different proteins have recently been identified, and a number of potential new markers of diseases have been characterized. Here, examples of the enormous promise of plasma/serum proteomic analysis for diagnostic/prognostic markers and information on disease mechanism are given. Within the blood are also a large number of different blood cell types that potentially hold similar information. Proteomics of red blood cells, until now, has not improved our knowledge of these cells, in contrast to the major progresses achieved while studying platelets and leukocytes. In the future, proteomics will change several aspects of hematology.

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Section: Leukocytesmentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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“…This association relies on both ephrin-B1 tyrosine phosphorylation and Lck activity. Signaling complexes localized to lipid rafts play an important role in the multiple aspects of T-cell biology (61)(62)(63) and our experiments reveal that ephrin-B1 modifies the composition of raft-interacting signaling molecules in malignant T lymphocytes, attracting the Rac1, and CrkL cytoskeletal regulators into lipid rafts, and induces strong repulsive responses in T-ALL cells. Unlike other proteins controlled by ephrin-B1 in lipid rafts (13), Rac1 and CrkL do not possess PDZ domains and their relocalization occurs in an Lck-dependent manner, representing a novel mechanism of ephrin-B1 action.…”

Section: Introductionmentioning

confidence: 99%

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Jiang

Freywald

Webster

et al. 2008

Molecular Cancer Research

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Proteins of the ephrin-B group operate in nonlymphoid cells through the control of their migration and attachment, and are crucial for the development of the vascular, lymphatic, and nervous systems. Ephrin-B activity is deregulated in various nonlymphoid malignancies; however, their precise role in cancer has only started to be addressed. We show here that ephrin-B1, a member of the ephrin-B group, is expressed in pediatric T-cell leukemias, including leukemia cell line Jurkat. Treatment of Jurkat cells with ephrin-Bstimulating EphB3 enhances ephrin-B1 phosphorylation and induces its relocalization into lipid rafts. These events are mediated by the T lineage -specific kinase, Lck, as ephrin-B1 phosphorylation and lipid raft association are blocked in the Lck-deficient clone of Jurkat, JCAM1.6. Ephrin-B1 also induces colocalization of the CrkL and Rac1 cytoskeleton regulators and initiates in leukemic cells a strong repulsive response. The absence of Lck blocks ephrin-B1 -induced signaling and repulsion, confirming the essential role for Lck in ephrin-B1 -mediated responses. This shows a new role for ephrin-B1 in the regulation of leukemic cells through the Lck-dependent Rac1 colocalization with its signaling partner, CrkL, in lipid rafts. In agreement with its repulsive action, ephrin-B1 seems to support metastatic properties of leukemic cells, as suppression of ephrin-B1 signaling inhibits their invasiveness. Because ephrin-B1 -activating EphB proteins are ubiquitously expressed, our findings suggest that ephrin-B1 is likely to play an important role in the regulation of malignant T lymphocytes through the control of lipid-raftassociated signaling, adhesion, and invasive activity, and therefore may represent a novel target for cancer treatment. (Mol Cancer Res 2008;6(2):291 -305)

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“…A number of transmembrane receptors are preferentially associated with lipid rafts, which have been postulated to serve as scaffolds on which signaling molecules assemble (Razzaq et al, 2004). The three probes used above, GPI-linked YFP, cholera toxin bound to GM1 gangliosides, and PM-GFP, are all believed to reside predominantly in lipid rafts.…”

Section: Segregation Of Lipid Microdomains Fails To Account For Membrmentioning

confidence: 99%

Quantitative Analysis of Membrane Remodeling at the Phagocytic Cup

Lee

Mason

Schreiber

et al. 2007

MBoC

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Nascent phagosomes, which are derived from the plasma membrane, acquire microbicidal properties through multiple fusion and fission events collectively known as maturation. Here we show that remodeling of the phagosomal membrane is apparent even before sealing, particularly when large particles are ingested. Fluorescent probes targeted to the plasma membrane are cleared from the region lining the particle before engulfment is completed. Extensive clearance was noted for components of the inner as well as outer monolayer of the plasmalemma. Segregation of lipid microdomains was ruled out as the mechanism underlying membrane remodeling, because markers residing in rafts and those that are excluded were similarly depleted. Selective endocytosis was also ruled out. Instead, several lines of evidence indicate that endomembranes inserted by exocytosis at sites of ingestion displace the original membrane constituents from the base of the phagosomal cup. The Fc␥ receptors that trigger phagocytosis remain associated with their ligands. By contrast, Src-family kinases that are the immediate effectors of receptor activation are flushed away from the cup by the incoming membranes. Together with the depletion of phosphoinositides required for signal transduction, the disengagement of receptors from their effectors by bulk membrane remodeling provides a novel means to terminate receptor signaling.

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Regulation of T‐cell receptor signalling by membrane microdomains

Cited by 86 publications

References 186 publications

Recent advances in blood‐related proteomics

Recent advances in blood‐related proteomics

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Quantitative Analysis of Membrane Remodeling at the Phagocytic Cup

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