Differential-expression and tyrosine-phosphorylation profiles of caveolin isoforms in human T cell leukemia cell lines

Tsuji, Yuichiro; Hatanaka, Minoru; Maeda, Takuya; Seya, Tsukasa; Takenaka, Hiroshi; Shimizu, Akira

doi:10.3892/ijmm.16.5.889

Cited by 5 publications

(13 citation statements)

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“…However, we demonstrate here that primary human T cells, Jurkat cells, and the constitutively polarized Peer T cells, contain caveolin‐1, which is found in lipid raft fractions of Peer T cells. In line with our data, the results from other groups obtained by using several specific Abs indicate that different T cell lines also contain caveolin‐1 25, 26.…”

Section: Discussionsupporting

confidence: 92%

“…It is generally accepted that caveolae are not present in lymphocytes due to their lack of caveolin expression 23, 24. However, the expression of caveolin‐1 in some human leukemia T‐cell lines that show a polarized‐activated phenotype has been demonstrated by the use of specific Abs 25, 26. To clarify whether T lymphocytes express caveolin‐1, we carried out RT‐PCR analysis using specific pairs of primers to amplify human caveolin‐1 from cDNAs prepared from primary human T lymphoblast and Jurkat and Peer T‐cells lines.…”

Section: Resultsmentioning

confidence: 99%

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The neuronal protein Kidins220/ARMS associates with ICAM‐3 and other uropod components and regulates T‐cell motility

et al. 2011

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Kinase D interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a protein that is mainly expressed in brain and neural cells where its function is only starting to be characterized. Here, we show that Kidins220/ARMS is also expressed in T lymphocytes where it is highly concentrated at the uropod of polarized T cells. In this cellular model, Kidins220/ARMS colocalizes with typical uropod T-cell molecules and coimmunoprecipitates with ICAM-3. Furthermore, Kidins220/ARMS associates with raft domains at the uropod and coimmunoprecipitates with caveolin-1, a molecule we show here to be also expressed in T cells. Importantly, induction of morphological polarization in primary T lymphocytes and Jurkat cells enhances Kidins220/ARMS colocalization with ICAM-3. Conversely, disruption of cell polarity provokes Kidins220/ARMS redistribution from the uropod to other cellular regions and drastically impairs its association with ICAM-3 in a protein kinase C-dependent manner. Finally, Kidins220/ARMS knockdown in human polarized T-cell lines promotes both basal and stromal cell-derived factor-1a-induced directed migration, identifying a novel function for this molecule. Altogether, our findings show that Kidins220/ARMS is a novel component of the uropod involved in the regulation of T-cell motility, an essential process for the immune response.Keywords: Cell migration . ICAM-3 . Kidins220/ARMS . T cells . Uropod Supporting Information available online Ã These authors have contributed equally to this study. IntroductionKinase D interacting substrate of 220 kDa (Kidins220) [1], also known as ankyrin repeat-rich membrane spanning, (ARMS) [2], is an integral membrane protein whose function remains widely unexplored. Kidins220/ARMS was identified in neuronal cells as the first physiological substrate for protein kinase D (PKD), and as a downstream effector of neurotrophin and ephrin receptors. The amino acid sequence of Kidins220/ARMS contains several structural and functional domains and diverse motifs that may potentially link this protein to membranes, cytoskeleton, and different signaling pathways. Kidins220/ARMS is predominantly expressed in brain and neural cells [1,2]. Neurons present a polarized phenotype and a differential distribution of specific molecules along the surfaces of the dendrites, the cell body, and the axonal projection [3]. The segregation and stabilization of many of these molecules to specific cellular subdomains is believed to be regulated in neurons and other polarized cells by the cytoskeleton [4]. It has been recently shown that in hippocampal neurons Kidins220/ARMS modulates the activity of microtubule-regulating proteins and controls neuronal polarity, development, and maturation [5].Resting T lymphocytes are largely spherical nonpolarized cells that upon activation, in response to chemoattractant and other stimuli, undergo morphological and cytoskeletal rearrangements and acquire a polarized morphology that confers them the ability to migrate [6,7...

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

The neuronal protein Kidins220/ARMS associates with ICAM‐3 and other uropod components and regulates T‐cell motility

et al. 2011

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“…Membrane-GR stimulation after Cav-1 silencing lead to a mild up-regulation of HADH, which was not observed in CCRF-CEM cells that do not express Cav-1. Thus, Cav-1 seems to act as a modulator of mGR activity and the outcome of mGR activation may ultimately depend on the relative numbers of mGR associated with Cav-1 or other members of the caveolin family, such as Cav-2 ␣, also expressed in leukemia T cells (61,62).…”

Section: Discussionmentioning

confidence: 99%

Membrane Glucocorticoid Receptor Activation Induces Proteomic Changes Aligning with Classical Glucocorticoid Effects

Vernocchi

Battello

Schmitz

et al. 2013

Molecular & Cellular Proteomics

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Glucocorticoids exert rapid nongenomic effects by several mechanisms including the activation of a membranebound glucocorticoid receptor (mGR). Here, we report the first proteomic study on the effects of mGR activation by BSA-conjugated cortisol (Cort-BSA). A subset of target proteins in the proteomic data set was validated by Western blot and we found them responding to mGR activation by BSA-conjugated cortisol in three additional cell lines, indicating a conserved effect in cells originating from different tissues. Changes in the proteome of BSA-conjugated cortisol treated CCRF-CEM leukemia cells were associated with early and rapid pro-apoptotic, immunemodulatory and metabolic effects aligning with and possibly "priming" classical activities of the cytosolic glucocorticoid receptor (cGR). PCR arrays investigating target genes of the major signaling pathways indicated that the mGR does not exert its effects through the transcriptional activity of any of the most common kinases in these leukemic cells, but RhoA signaling emerged from our pathway analysis. All cell lines tested displayed very low levels of mGR on their surface. Highly sensitive and specific in situ proximity ligation assay visualized low numbers of mGR even in cells previously thought to be mGR negative. We obtained similar results when using three distinct anti-GR monoclonal antibodies directed against the N-terminal half of the cGR. This strongly suggests that the mGR and the cGR have a high sequence homology and most probably originate from the same gene. Furthermore, the mGR appears to reside in caveolae and its association with caveolin-1 (Cav-1) was clearly detected in two of the four cell lines investigated using double recognition proximity ligation assay. Our results indicate however that Cav-1 is not necessary for membrane localization of the GR since CCRF-CEM and Jurkat cells have a functional mGR, but did not express this caveolar protein. However, if expressed, this membrane protein dimerizes with the mGR modulating its function. Molecular & Cellular

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“…Alternatively, the relatively low expression levels in T lineage cells may account for the reported lack of detection using less sensitive techniques. More recent evidence has shown that caveolin-1 is expressed in other immune cells including murine macrophages and mast cells (41), human and bovine dendritic cells (41), murine B cells (42), human, rat and murine neutrophils (41), activated T cell leukemia lines (43, 44), and bovine T cells (41). Additional expression profiling in thymocyte and effector T subsets will be necessary to determine if all T lineage cells express caveolin-1 or whether varying levels of caveolin-1 throughout development might function as a mechanism of setting subset-specific TCR thresholds or membrane trafficking.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Orchestrates TCR Synaptic Polarity, Signal Specificity, and Function in CD8 T Cells

Tomassian

Humphries

Liu

et al. 2011

The Journal of Immunology

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TCR engagement triggers the polarized recruitment of membrane, actin, and transducer assemblies within the T cell–APC contact that amplify and specify signaling cascades and Teffector activity. We report that caveolin-1, a scaffold that regulates polarity and signaling in nonlymphoid cells, is required for optimal TCR-induced actin polymerization, synaptic membrane raft polarity, and function in CD8, but not CD4, T cells. In CD8+ T cells, caveolin-1 ablation selectively impaired TCR-induced NFAT-dependent NFATc1 and cytokine gene expression, whereas caveolin-1 re-expression promoted NFATc1 gene expression. Alternatively, caveolin-1 ablation did not affect TCR-induced NF-κB–dependent Iκbα expression. Cav-1−/− mice did not efficiently promote CD8 immunity to lymphocytic choriomeningitis virus, nor did cav-1−/− OT-1+ CD8+ T cells efficiently respond to Listeria mono-cytogenes-OVA after transfer into wild-type hosts. Therefore, caveolin-1 is a T cell-intrinsic orchestrator of TCR-mediated membrane polarity and signal specificity selectively employed by CD8 T cells to customize TCR responsiveness.

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Differential-expression and tyrosine-phosphorylation profiles of caveolin isoforms in human T cell leukemia cell lines

Cited by 5 publications

References 0 publications

The neuronal protein Kidins220/ARMS associates with ICAM‐3 and other uropod components and regulates T‐cell motility

The neuronal protein Kidins220/ARMS associates with ICAM‐3 and other uropod components and regulates T‐cell motility

Membrane Glucocorticoid Receptor Activation Induces Proteomic Changes Aligning with Classical Glucocorticoid Effects

Caveolin-1 Orchestrates TCR Synaptic Polarity, Signal Specificity, and Function in CD8 T Cells

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