Copper as a key regulator of cell signalling pathways

Author(s):  
Alexandra Grubman ◽  
Anthony R. White

Copper is an essential element in many biological processes. The critical functions associated with copper have resulted from evolutionary harnessing of its potent redox activity. This same property also places copper in a unique role as a key modulator of cell signal transduction pathways. These pathways are the complex sequence of molecular interactions that drive all cellular mechanisms and are often associated with the interplay of key enzymes including kinases and phosphatases but also including intracellular changes in pools of smaller molecules. A growing body of evidence is beginning to delineate the how, when and where of copper-mediated control over cell signal transduction. This has been driven by research demonstrating critical changes to copper homeostasis in many disorders including cancer and neurodegeneration and therapeutic potential through control of disease-associated cell signalling changes by modulation of copper–protein interactions. This timely review brings together for the first time the diverse actions of copper as a key regulator of cell signalling pathways and discusses the potential strategies for controlling disease-associated signalling processes using copper modulators. It is hoped that this review will provide a valuable insight into copper as a key signal regulator and stimulate further research to promote our understanding of copper in disease and therapy.

1998 ◽  
Vol 353 (1374) ◽  
pp. 1489-1494 ◽  
Author(s):  
Alistair M. Hetherington ◽  
Julie E. Gray ◽  
Calum P. Leckie ◽  
Martin R. McAinsh ◽  
Carl Ng ◽  
...  

Stomatal guard cells have proven to be an attractive system for dissecting the mechanisms of stimulus–response coupling in plants. In this review we focus on the intracellular signal transduction pathways by which extracellular signals bring about closure and opening of the stomatal pore. It is proposed that guard cell signal transduction pathways may be organized into functional arrays or signalling cassettes that contain elements common to a number of converging signalling pathways. The purpose of these signalling cassettes may be to funnel extracellular signals down onto the ion transporters that control the fluxes of ions that underlie stomatal movements. Evidence is emerging that specificity in guard cell signalling may be, in part, encoded in complex spatio–temporal patterns of increases in the concentration of cytosolic–free calcium ([Ca 2+ ] cyt ). It is suggested that oscillations in [Ca 2+ ] cyt may generate calcium signatures that encode information concerning the stimulus type and strength. New evidence is presented that suggests that these calcium signatures may integrate information when many stimuli are present.


1998 ◽  
Vol 143 (3) ◽  
pp. 637-644 ◽  
Author(s):  
Thomas M. Stulnig ◽  
Markus Berger ◽  
Thomas Sigmund ◽  
Daniel Raederstorff ◽  
Hannes Stockinger ◽  
...  

Polyunsaturated fatty acids (PUFAs) exert immunosuppressive effects, but the molecular alterations leading to T cell inhibition are not yet elucidated. Signal transduction seems to involve detergent-resistant membrane domains (DRMs) acting as functional rafts within the plasma membrane bilayer with Src family protein tyrosine kinases being attached to their cytoplasmic leaflet. Since DRMs include predominantly saturated fatty acyl moieties, we investigated whether PUFAs could affect T cell signaling by remodeling of DRMs. Jurkat T cells cultured in PUFA-supplemented medium showed a markedly diminished calcium response when stimulated via the transmembrane CD3 complex or glycosyl phosphatidylinositol (GPI)- anchored CD59. Immunofluorescence studies indicated that CD59 but not Src family protein tyrosine kinase Lck remained in a punctate pattern after PUFA enrichment. Analysis of DRMs revealed a marked displacement of Src family kinases (Lck, Fyn) from DRMs derived from PUFA-enriched T cells compared with controls, and the presence of Lck in DRMs strictly correlated with calcium signaling. In contrast, GPI-anchored proteins (CD59, CD48) and ganglioside GM1, both residing in the outer membrane leaflet, remained in the DRM fraction. In conclusion, PUFA enrichment selectively modifies the cytoplasmic layer of DRMs and this alteration could underlie the inhibition of T cell signal transduction by PUFAs.


ChemBioChem ◽  
2015 ◽  
Vol 16 (4) ◽  
pp. 602-610 ◽  
Author(s):  
J. Joris Witsenburg ◽  
Michael D. Sinzinger ◽  
Oda Stoevesandt ◽  
Ivo R. Ruttekolk ◽  
Günter Roth ◽  
...  

2006 ◽  
Vol 18 (4) ◽  
pp. 199-206 ◽  
Author(s):  
Shimon Sakaguchi ◽  
Noriko Sakaguchi ◽  
Hiroyuki Yoshitomi ◽  
Hiroshi Hata ◽  
Takeshi Takahashi ◽  
...  

FEBS Letters ◽  
2010 ◽  
Vol 584 (11) ◽  
pp. 2455-2460 ◽  
Author(s):  
Geoffrey Guittard ◽  
Eva Mortier ◽  
Hélène Tronchère ◽  
Guylène Firaguay ◽  
Audrey Gérard ◽  
...  

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