Identification of (<i>E</i>)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate as a major activator for human γδ T cells in <i>Escherichia coli</i>

Hintz, Martin; Reichenberg, Armin; Altincicek, Boran; Bahr, U.; Gschwind, Ruth M.; Kollas, Ann-Kristin; Beck, Ewald; Wiesner, Jochen; Eberl, Matthias; Jomaa, Hassan

doi:10.1016/s0014-5793(01)03191-x

Cited by 317 publications

(299 citation statements)

References 37 publications

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“…The shoot localization of the iPMP-independent pathway may be explained in terms of exclusive access of the side-chain donor in green plant tissue. The putative side-chain precursor, (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate, has been identified as a key intermediate in the 2-C-methyl-D-erythritol 4-phosphate pathway of terpenoid biosynthesis (37). This pathway, initially detected in prokaryotes, is expressed in eukaryotes that harbor plastids within their cells (38).…”

Section: Discussionmentioning

confidence: 99%

Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana : A factor of potential importance for auxin–cytokinin-regulated development

Nordström

Tarkowski

Tarkowská

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

510

397

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One of the most long-lived models in plant science is the belief that the long-distance transport and ratio of two plant hormones, auxin and cytokinin, at the site of action control major developmental events such as apical dominance. We have used in vivo deuterium labeling and mass spectrometry to investigate the dynamics of homeostatic cross talk between the two plant hormones. Interestingly, auxin mediates a very rapid negative control of the cytokinin pool by mainly suppressing the biosynthesis via the isopentenyladenosine-5 -monophosphate-independent pathway. In contrast, the effect of cytokinin overproduction on the entire auxin pool in the plant was slower, indicating that this most likely is mediated through altered development. In addition, we were able to confirm that the lateral root meristems are likely to be the main sites of isopentenyladenosine-5 -monophosphate-dependent cytokinin synthesis, and that the aerial tissue of the plant surprisingly also was a significant source of cytokinin biosynthesis. Our demonstration of shoot-localized synthesis, together with data demonstrating that auxin imposes a very rapid regulation of cytokinin biosynthesis, illustrates that the two hormones can interact also on the metabolic level in controlling plant development, and that the aerial part of the plant has the capacity to synthesize its own cytokinin independent of long-range transport from the root system.

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Section: Discussionmentioning

confidence: 99%

Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana : A factor of potential importance for auxin–cytokinin-regulated development

Nordström

Tarkowski

Tarkowská

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

510

397

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“…6 Endogenously, IPP and its stereoisomer dimethylallyl diphosphate are substrates produced in the mevalonate pathway for cholesterol metabolism; however, they can also be produced by the deoxyxylulose pathway commonly used by organisms, such as Escherichia coli and certain plant cells, that lack the critical HMGCoA reductase enzyme of the mevalonate pathway. 65,66 It was later determined that the stimulatory capacity of IPP and dimethylallyl diphosphate is actually fairly weak in comparison to some of the upstream intermediates of the alternative pathway of isoprenoid biosynthesis, such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate, 67 and it is usually in the context of malignancy or distress that cellular endogenous levels are able to awaken the effector functions of Vc9Vd2 T cells. 68 A class of drugs called aminobisphosphonates used for the prevention of bone fragility fractures and certain alkylamine compounds that are ubiquitously dispersed in everything from plants to amniotic fluid are also able to stimulate Vc9Vd2 T cells 69,70 by virtue of their ability to induce cellular accumulation of IPP.…”

Section: Vd2 T Cells: To Know the Complex Burden Of Being Humanmentioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

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“…V␥2V␦2 T cells constitute 60-95% of circulating human ␥␦ T cells and are unique in their ability to massively expand during various bacterial and protozoal infections (9). V␥2V␦2 T cell expansion appears to be specifically mediated by certain low molecular weight foreign-and selfnonpeptidic phosphorylated metabolites of isoprenoid biosynthesis [e.g., (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), isopentenyl pyrophosphate, and its isomer dimethylallyl pyrophosphate] (10)(11)(12). HMBPP is produced in the newly-discovered 2-C-methyl-D-erythritol-4-phosphate pathway of isoprenoid biosynthesis of most eubacteria, apicomplexan protozoa, plant chloroplasts, and algae but not in vertebrates and thus normally not in the human host (13).…”

Section: The Possibility That V␥2v␦2 T Effector Cells Can Confer Protmentioning

confidence: 99%

Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions

Huang

Chen

Ali

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Identification of (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate as a major activator for human γδ T cells in Escherichia coli

Cited by 317 publications

References 37 publications

Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana : A factor of potential importance for auxin–cytokinin-regulated development

Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana : A factor of potential importance for auxin–cytokinin-regulated development

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions

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