The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling.

Jayaraman, Thottala; Ondriašová, Elena; Ondriaš, Karol; Harnick, David J.; Marks, Andrew R.

doi:10.1073/pnas.92.13.6007

Cited by 133 publications

(119 citation statements)

References 36 publications

(25 reference statements)

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“…Several models for Ca 2ϩ channels in the plasma membrane of T lymphocytes have been proposed, including IP 3 receptor (IP 3 R) Ca 2ϩ channels, mammalian homologues of transient receptor potential (TRP) Ca 2ϩ channels, and L-type voltage-dependent Ca 2ϩ channels (VDCCs). Initially, investigators suggested that a plasma membrane IP 3 R Ca 2ϩ channel, similar to the IP 3 R found in the ER, was responsible for Ca 2ϩ influx in T lymphocytes (9). A recent study confirmed that T lymphocytes express three isoforms of the IP 3 R Ca 2ϩ channel as integral plasma membrane proteins (10).…”

mentioning

confidence: 72%

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Kotturi¹,

Carlow²,

Lee³

et al. 2003

Journal of Biological Chemistry

101

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In T lymphocytes, sustained calcium (Ca 2؉ ) influx through Ca 2؉ channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca 2؉ channels (VDCCs) play a role in Ca 2؉ mobilization during T lymphocyte activation. However, the role of VDCCs in otherwise nonexcitable cells is still poorly understood. We used RT-PCR to identify a transcript encoding the pore-forming ␣ 1F -subunit of an L-type Ca 2؉ channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca 2؉ influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca 2؉ channel agonist, (؉/؊) Bay K 8644, and antagonist, nifedipine, on the human Jurkat T cell leukemia line, human peripheral blood T lymphocytes and mouse splenocytes. We found that treatment of T lymphocytes with (؉/؊) Bay K 8644 increased intracellular Ca 2؉ and induced the activation of phosphoextracellular-regulated kinase 1/2 (Erk1/2), whereas nifedipine blocked Ca 2؉ influx, the activity of Erk1/2 and nuclear factor of activated T cells (NFAT), interleukin-2 (IL-2) production, and IL-2 receptor expression. Nifedipine also significantly suppressed splenocyte proliferation in an in vitro mixed lymphocyte reaction and the proliferation of male antigen (H-Y)-specific T cell receptor-transgenic CD8 ؉ T cells in transplanted male mice in vivo. Taken together these novel findings indicate that an L-type Ca 2؉ channel plays a significant role in the Ca 2؉ influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo.

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mentioning

confidence: 72%

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Kotturi¹,

Carlow²,

Lee³

et al. 2003

Journal of Biological Chemistry

101

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“…Such a systematic apposition has not been described in electronic microscopy studies. Furthermore, in IP 3 Rdeficient cells, ionomycin or thapsigargin are perfectly efficient in eliciting a capacitative Ca 2+ entry (Broad et al, 2001;Jayaraman et al, 1995).…”

Section: Ca 2+ Influxmentioning

confidence: 99%

Ca²⁺ signals and T lymphocytes “New mechanisms and functions in Ca²⁺ signalling”

Randriamampita

Trautmann

2004

Biology of the Cell

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Interaction between a T cell and an antigen-presenting cell leads to the rapid formation of an immunological synapse allowing antigen detection by the T cell and the development of an immune response. Antigen detection triggers various cellular responses including a modest but sustained T cell Ca 2+ increase. In this review are discussed a series of related questions. What are the various molecular events by which a T cell Ca 2+ response can be triggered in the immunological synapse by a very small amount of antigen ? How is Ca 2+ released from intracellular stores and how can these stores remain empty for hours ? Through which channels does Ca 2+ influx takes place, and how is Ca 2+ influx coupled to Ca 2+ release from intracellular stores ? What are the main immediate and indirect cellular targets of the Ca 2+ increase ?

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“…IP 3 Rs dominantly control the initiation of IP 3 -induced calcium release, demonstrated by using antisense knockdown of IP 3 R to block calcium release from the ER (20). Jurkat T cells express three IP 3 R isoforms, IP 3 R-1, IP 3 R-2, and IP 3 R-3 (21), which differ significantly in their sensitivity to IP 3 (22,23).…”

mentioning

confidence: 99%

The Calponin Homology Domain of Vav1 Associates with Calmodulin and Is Prerequisite to T Cell Antigen Receptor-induced Calcium Release in Jurkat T Lymphocytes

Zhou¹,

Yin²,

Dou

et al. 2007

Journal of Biological Chemistry

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Vav1 is a guanine nucleotide exchange factor that is expressed specifically in hematopoietic cells and plays important roles in T cell development and activation. Vav1 consists of multiple structural domains so as to facilitate both its guanine nucleotide exchange activity and scaffold function following T cell antigen receptor ( Stimulation of the T cell antigen receptor (TCR)2 initiates a cascade of signaling events that lead to T cell activation. Calcium plays a central role in this process and has been studied intensively (1-4). Engagement of TCR triggers the activation and accumulation of enzymes and adapter molecules to the proximal membrane (5, 6), such as tyrosine phosphorylation and activation of phospholipase-C␥1 (PLC-␥1), thereby increasing the production of inositol 1,4,5-trisphosphate (IP 3 ). IP 3 binds to and activates the inositol 1,4,5-trisphosphate receptor (IP 3 R), which results in Ca 2ϩ release from the endoplasmic reticulum (ER) and the subsequent calcium influx from Ca 2ϩ release-activated Ca 2ϩ channel (CRAC) (1, 7). The elevated cytoplasmic [Ca 2ϩ ] i evokes a multitude of cellular responses, such as the NFAT-mediated gene expressions and the cell proliferation (8, 9).Vav1 is expressed specifically in hematopoietic cells as a 95-kDa protein, which plays pivotal roles as a guanine exchange factor (GEF) for small GTPases as well as a scaffold protein in the activation of hematopoietic cells (10 -12). The importance of Vav1 is because of its multiple structural elements, including a calponin homology (CH) domain, an acidic motif, a Dbl homology domain, a pleckstrin homology (PH) domain, a cysteine-rich motif, and one single SH2 domain flanked by two SH3 domains responsible for signaling protein assembly (12, 13). Upon TCR engagement, Vav1 is phosphorylated on the key tyrosine residues in the acidic motif, leading to the exposure of active Dbl homology domain for GDP/GTP exchange activity (14). Studies on vav1 Ϫ/Ϫ T cells isolated from knock-out mice demonstrated that Vav1 is essential for normal T cell activation and proliferation (15)(16)(17). In addition, the vav1-null cell line, J.Vav1, derived from Jurkat cells by somatic gene targeting approach, also exhibits pleiotropic defects in TCR-mediated signaling pathways (18).T cell stimulation evokes a biphasic calcium flux as follows: calcium release from intracellular stores followed by calcium influx across the plasma membrane (7,19). IP 3 Rs dominantly control the initiation of IP 3 -induced calcium release, demonstrated by using antisense knockdown of IP 3 R to block calcium release from the ER (20). Jurkat T cells express three IP 3 R isoforms, IP 3 R-1, IP 3 R-2, and IP 3 R-3 (21), which differ significantly in their sensitivity to IP 3 (22,23). A tyrosine kinase, Fyn, was suggested to modulate IP 3 R channel activities (24,25). Interactions between IP 3 R and other proteins, such as calmodulin (CaM), were reported to control the channel opening. Although some observations viewed CaM as an inhibitory protein of IP 3 R (26 -28), more...

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The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling.

Abstract: Antigen-specific activation ofT lymphocytes, via stimulation of the T-cell antigen receptor (TCR)

Cited by 133 publications

References 36 publications

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Ca²⁺ signals and T lymphocytes “New mechanisms and functions in Ca²⁺ signalling”

The Calponin Homology Domain of Vav1 Associates with Calmodulin and Is Prerequisite to T Cell Antigen Receptor-induced Calcium Release in Jurkat T Lymphocytes

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The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling.

Abstract: Antigen-specific activation ofT lymphocytes, via stimulation of the T-cell antigen receptor (TCR)

Cited by 133 publications

References 36 publications

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Ca2+ signals and T lymphocytes “New mechanisms and functions in Ca2+ signalling”

The Calponin Homology Domain of Vav1 Associates with Calmodulin and Is Prerequisite to T Cell Antigen Receptor-induced Calcium Release in Jurkat T Lymphocytes

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Ca²⁺ signals and T lymphocytes “New mechanisms and functions in Ca²⁺ signalling”