T Cell Antigen Receptor-Mediated Activation of Phospholipase C Requires Tyrosine Phosphorylation

Mustelin, Tomas; Coggeshall, K. Mark; Isakov, Noah; Altman, Amnon

doi:10.1126/science.2138816

Cited by 435 publications

(184 citation statements)

References 38 publications

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“…These include (1) immunoblotting of DGK~ using anti-phosphotyrosine and -phosphoserine antibodies, (2) isoelectrofocusing of the cell extracts in urea-containing gels followed by immunoblotting with anti-DGKa antibody, and (3) side-by-side comparison of the mobility of the enzyme proteins upon Western blotting. We therefore concluded that protein kinases known to be activated immediately after the TcR occupancy [15,16], were not directly involved in the DGKc~ translocation. The present work suggests a novel function of DGKa in nuclear phospholipid metabolism, although the mechanism of its translocation to the nucleus could not be elucidated.…”

Section: Resultsmentioning

confidence: 85%

“…The activation of the T-cell receptor (TcR)/CD3 complex initially results in tyrosine phosphorylation of a number of proteins followed immediately by phosphoinositide turnover [15,16]. This initial signal transduction is followed at the second stage by the expression at the cell surface of high-affinity interleukin (IL)-2 receptors [17].…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

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Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

et al. 1996

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The cytosolic ~-diacylglycerol kinase (DGK) was translocated to and tightly associated with the nuclear matrix when rat thymocytes and peripheral T-lymphocytes were stimulated with concanavalin A or anti-T-cell receptor antibody. This translocation occurred rather slowly and was completed in 3-4 h after cell stimulation. We also detected significant accumulation of nuclear phosphatidic acid interpreted as being formed by the translocated enzyme. The enzyme translocation is not directly linked to pbospboinositide turnover and protein pbospborylation, since pborbol myristate acetate and calcium ionopbore did not affect the cellular DGK(x and since we detected no covalent modification of the enzyme molecule. Although the mechanisms underlying the enzyme translocation remain unknown, our results indicate that DGKcx participates in nuclear pbospbollpid metabolism occurring at the intermediate stage of lymphocyte activation.Key words." Diacylglycerol kinase, c~-isozyme; T-lymphocyte, rat; Translocation; Nuclear matrix elucidated by the finding that DGKa could account for the most of the DGK activity, which was rapidly increased after IL-2 stimulation of T-cell lines [18]. However, the role of DGKc~ in phosphoinositide turnover and in other biochemical events preceding the expression of IL-2 receptors remains unknown. For example, exogenous short-chain DG repeatedly administered to human T-lymphocytes was phosphorylated by cellular DGK only to a negligible extent [19]. Van der Bend et al. [20] proposed a topological sequestration of cellular DGK molecules based on the finding that DG artificially generated by treating Jurkat and other cells with bacterial phospholipase C could not serve as substrate for the cellular DGK. These observations indicate that the metabolic role of DGKa abundantly contained in T-lymphocytes is still largely unknown and that the cellular DGKs are operating under strict control mechanisms. Here we describe a targeting of DGKc~ to the nuclear matrix upon T-cell activation and suggest the participation of this DGK isozyme in the nuclear phospholipid metabolism occurring in stimulated lymphocytes.

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Section: Resultsmentioning

confidence: 85%

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

et al. 1996

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“…Following mechanical disruption of splenocytes on a wire mesh screen, RBC were removed by osmotic lysis in ACK buffer (NH 4 Cl, KHCO 3 , and EDTA). Splenocytes were then resuspended in RPMI 1640 supplemented with 10% FCS, L-glutamine, penicillin-streptomycin, and 2-ME (complete medium).…”

Section: Cell Isolation and Mediummentioning

confidence: 99%

The Requirement of Reversible Cysteine Sulfenic Acid Formation for T Cell Activation and Function

Michalek

Nelson

Holbrook

et al. 2007

The Journal of Immunology

100

101

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Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in mediating cellular responses. We have examined the importance of reversible cysteine sulfenic acid formation in naive CD8+ T cell activation and proliferation. We observed that, within minutes of T cell activation, naive CD8+ T cells increased ROI levels in a manner dependent upon Ag concentration. Increased ROI resulted in elevated levels of cysteine sulfenic acid in the total proteome. Analysis of specific proteins revealed that the protein tyrosine phosphatases SHP-1 and SHP-2, as well as actin, underwent increased sulfenic acid modification following stimulation. To examine the contribution of reversible cysteine sulfenic acid formation to T cell activation, increasing concentrations of 5,5-dimethyl-1,3-cyclohexanedione (dimedone), which covalently binds to cysteine sulfenic acid, were added to cultures. Subsequent experiments demonstrated that the reversible formation of cysteine sulfenic acid was critical for ERK1/2 phosphorylation, calcium flux, cell growth, and proliferation of naive CD8+ and CD4+ T cells. We also found that TNF-α production by effector and memory CD8+ T cells was more sensitive to the inhibition of reversible cysteine sulfenic acid formation than IFN-γ. Together, these results demonstrate that reversible cysteine sulfenic acid formation is an important regulatory mechanism by which CD8+ T cells are able to modulate signaling, proliferation, and function.

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“…For several years it appeared that the early events of T lymphocyte activation paralleled those of several receptor-mediated, Ca++-dependent, activation schemes that involve Gprotein activation of a phospholipase C that catalyzes the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers, InsP3 and DAG (Berridge and Irvine, 1984). However, several recent studies have emphasized the role of tyrosine phosphorylation events in T lymphocyte activation (June et aL, 1990;Mustelin et al, 1990;Samelson et al, 1990), and two recent studies have cast doubt on the necessity of phosphoinositide hydrolysis for T lymphocyte activation. In a T-cell hybridoma carrying transfected TCR chains, interleukin 2 (IL-2) production in response to antigen and anti-CD3 monoclonal antibodies (MAb), comparable with that in the parent T-cell line, occurred despite much reduced production of inositol phosphates (Sussman et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Activation of phospholipase D: a signaling system set in motion by perturbation of the T lymphocyte antigen receptor/CD3 complex.

et al. 1991

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A number of cellular signaling systems are called into play by interaction of the T lymphocyte antigen receptor/CD3 complex with its cognate antigen. Well-described signaling systems include phosphoinositide turnover, tyrosine phosphorylation, protein kinase C activation, and increased cytosolic calcium. We have explored the possibility that another recently described signaling system, activation of phospholipase D, may be operative. Data presented here demonstrate that stimulation of Jurkat T cells with anti-CD3 antibodies or phorbol esters resulted in activation of phospholipase D, as

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T Cell Antigen Receptor-Mediated Activation of Phospholipase C Requires Tyrosine Phosphorylation

Cited by 435 publications

References 38 publications

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

The Requirement of Reversible Cysteine Sulfenic Acid Formation for T Cell Activation and Function

Activation of phospholipase D: a signaling system set in motion by perturbation of the T lymphocyte antigen receptor/CD3 complex.

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