Role of p56lck and ZAP70-mediated tyrosine phosphorylation in galectin-1-induced cell death

Ion, Gabriela; Fajka‐Boja, Roberta; Tóth, Gábor; Caron, M; Monostori, Éva

doi:10.1038/sj.cdd.4401628

Cited by 44 publications

(60 citation statements)

References 8 publications

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“…The apoptotic effect of extracellular Gal-1 on activated T-cells has been described in a number of papers [3,4,6,24,30]. It has also been shown that T-cells express Gal-1 upon activation.…”

Section: Discussionmentioning

confidence: 99%

“…Even though the signaling pathways responsible for exGal-1 driven T-cell apoptosis have largely been mapped [6,7,[36][37][38], many questions about the exact mechanism by which the cells were sensitized by inGal-1 to exGal-1 mediated apoptosis remain to be elucidated. While the anti-apoptotic effect of intracellular Gal-3 can be explained by the Bcl-2 homolog motif of the protein [39], Gal-1 does not have a homologous segment with any known apoptotic protein, and thus its function in apoptosis must stem from a yet unknown mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of Gal-1-triggered cell death has extensively been studied in vitro and presented by our group and others [4,5]. As it has been shown, stimulation of apoptosis requires the presence of p56lck and ZAP70 kinases, release of ceramide, decrease of mitochondrial membrane potential and caspase activation [4,6,7] and requires the direct interaction between T-cells and the surrounding environment (cells or extracellular matrix) [4]. Immunoregulatory function of Gal-1 has also been confirmed by in vivo experiments [5].…”

Section: Introductionmentioning

confidence: 99%

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Novel role for galectin-1 in T-cells under physiological and pathological conditions

Deák¹,

Hornung²,

Novák³

et al. 2015

Immunobiology

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Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated Tcells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus.

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“…The apoptotic effect of extracellular Gal-1 on activated T-cells has been described in a number of papers [3,4,6,24,30]. It has also been shown that T-cells express Gal-1 upon activation.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Deák¹,

Hornung²,

Novák³

et al. 2015

Immunobiology

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“…Медицинская Иммунология ных клеток, которые обладают фенотипом толе-рогенных и стимулируют экспансию регулятор-ных Т-лимфоцитов, секретирующих IL-10 [5,21,26]. Тучные клетки.…”

Section: якушина вд и дрunclassified

“…В от-ношении человеческих Т-лимфоцитов, находя-щихся в состоянии покоя, описана способность галектин-1 увеличивать чувствительность к FAS-индуцируемой/каспаз-8-опосредуемой клеточ-ной гибели, что сопровождается снижением трансмембранного потенциала митохондрий, выходом цитохрома с и активацией церамидно-го пути [33]. G. Ion et al (2005) объяснили выход цитохрома с и запуск митохондриального пути апоптоза активацией галектином-1 трансдук-ции сигнала через TCRζ/Lck/ZAP70 [22]. Боль-шинство работ, изучающих механизмы реализа-ции апоптоза, индуцированного галектином-1, проведены на различных клеточных линиях Т-лимфоцитов.…”

Section: Cd8unclassified

Galectin-1 and Its Role in Development of Innate and Adaptive Immunity

Yakushina¹,

Васильева²,

Рязанцева³

et al. 2014

Med. immunol.

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Общие данные о галектине-1, как представите-ле семейства галектиновБыстрота и информативность, с которой рас-ширяются наши представления о регуляции иммунологического гомеостаза в норме и при различной патологии, ярко иллюстрируется Галектин-1: роль в формировании оСоБенноСтеЙ вроЖДенноГо и ПриоБретенноГо иммУнитета Якушина В.Д., Васильева О.А., Рязанцева Н.В., Новицкий В.В., Савельева О.Е., Прохоренко Т.С., Старикова Е.Г., Зима А.П. ГБОУ ВПО Сибирский государственный медицинский университет Минздравсоцразвития России, г. ТомскРезюме. Галектины -это β-галактозид-связывающие белки, объединенные в одно семейство со-гласно гомологии их углевод-распознающего домена. Данные лектины связываются с гликанами клеточной поверхности и экстрацеллюлярного матрикса, оказывая, таким образом, влияние на кле-точный цикл, адгезию, миграцию, пролиферацию и апоптоз. Кроме того, галектины способны дей-ствовать внутриклеточно и принимать участие, например, в сигнальной трансдукции, взаимодействуя с другими белками цитоплазмы и ядра. В регуляции функциональной активности клеток иммунной системы особое значение отводится галектину-1. Данный белок, являясь фактором кооперации им-мунокомпетентных клеток, способен модулировать иммунные реакции. В связи с этим, галектин-1 рассматривается в качестве возможного агента или мишени для разработки новых методов коррек-ции патологических процессов, связанных с дисбалансом клеток иммунной системы. В данной ста-тье приводится обзор работ посвященных изучению роли галектина-1 в формировании особенностей врожденного и приобретенного иммунитета. GALECTIN-1 AND ITS ROLE IN DEVELOPMENT OF INNATE AND ADAPTIVE IMMUNITYAbstract. Galectins comprise a family of β-galactoside-binding animal proteins, which are defined by common homologies of their carbohydrate-recognizing domaine (affinity for poly-N-acetyllactosamine). These lectins bind to cell surface glycans and extracellular matrix, thus influencing various cellular events, including cell cycle, adhesion, migration, proliferation and apoptosis. Moreover, galectins are able to exert intracellular effects, and participate, e.g., in signal transduction, by interacting with other nuclear and cytoplasmic proteins. Galectin-1 is considered to play a special role in functional regulation of immune cell activity. Thus protein is a factor of immunocompetent cell cooperation, thus being able to modulate immune reactions. In this respect, galectin-1 is considered as a potential agent or a target for new methods aimed to correct pathological processes associated with imbalance of immune system. This article provides an overview of works devoted to a possible role of galectin-1 in development of typical features of innate and adaptive immunity.

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Galectin‐1–Asialofetuin Interaction Is Inhibited by Peptides Containing the Tyr‐Xxx‐Tyr Motif Acting on the Glycoprotein

et al. 2010

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Galectin-1 (Gal-1), a ubiquitous beta-galactoside-binding protein expressed by various normal and pathological tissues, has been implicated in cancer and autoimmune/inflammatory diseases in consequence of its regulatory role in adhesion, cell viability, proliferation, and angiogenesis. The functions of Gal-1 depend on its affinity for beta-galactoside-containing glycoconjugates; accordingly, the inhibition of sugar binding blocks its functions, hence promising potential therapeutic tools. The Tyr-Xxx-Tyr peptide motifs have been reported to be glycomimetic sequences, mainly on the basis of their inhibitory effect on the Gal-1-asialofetuin (ASF) interaction. However, the results regarding the efficacy of the Tyr-Xxx-Tyr motif as a glycomimetic inhibitor are still controversial. The present STD and trNOE NMR experiments reveal that the Tyr-Xxx-Tyr peptides studied do not bind to Gal-1, whereas their binding to ASF is clearly detected. (15)N,(1)H HSQC titrations with (15)N-labeled Gal-1 confirm the absence of any peptide-Gal-1 interaction. These data indicate that the Tyr-Xxx-Tyr peptides tested in this work are not glycomimetics as they interact with ASF via an unrevealed molecular linkage.

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Role of p56lck and ZAP70-mediated tyrosine phosphorylation in galectin-1-induced cell death

Cited by 44 publications

References 8 publications

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Galectin-1 and Its Role in Development of Innate and Adaptive Immunity

Galectin‐1–Asialofetuin Interaction Is Inhibited by Peptides Containing the Tyr‐Xxx‐Tyr Motif Acting on the Glycoprotein

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