Redox metabolism: ROS as specific molecular regulators of cell signaling and function

Cells constantly sense their environment, allowing the adaption of cell behavior to changing needs. Fine-tuned responses to complex inputs are computed by signaling pathways, which are wired in complex connected networks. Their activity is highly context-dependent, dynamic, and heterogeneous even between closely related individual cells. Despite lots of progress, our understanding of the precise implementation, relevance, and possible manipulation of cellular signaling in health and disease therefore remains limited. Here, we discuss the requirements, potential, and limitations of the different current technologies for the analysis of hematopoietic stem and progenitor cell signaling and its effect on cell fates.

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Characterizing how glycerol monolaurate (GML) affects human T cell signaling and function

10.17077/etd.mzucnvs8 ◽

2018 ◽

Author(s):

Michael Sining Zhang

Keyword(s):

T Cell ◽

Cell Signaling ◽

T Cell Signaling ◽

Human T Cell ◽

Glycerol Monolaurate ◽

And Function

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Induced transcription and stability of CELF2 mRNA drives widespread alternative splicing during T-cell signaling

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1423695112 ◽

2015 ◽

Vol 112 (17) ◽

pp. E2139-E2148 ◽

Cited By ~ 29

Author(s):

Michael J. Mallory ◽

Samuel J. Allon ◽

Jinsong Qiu ◽

Matthew R. Gazzara ◽

Iulia Tapescu ◽

...

Keyword(s):

Alternative Splicing ◽

T Cell ◽

Cell Signaling ◽

T Cell Development ◽

Cell Types ◽

Cell Development ◽

Mrna Processing ◽

Similar Proportion ◽

T Cell Signaling ◽

And Function

Studies in several cell types have highlighted dramatic and diverse changes in mRNA processing that occur upon cellular stimulation. However, the mechanisms and pathways that lead to regulated changes in mRNA processing remain poorly understood. Here we demonstrate that expression of the splicing factor CELF2 (CUGBP, Elav-like family member 2) is regulated in response to T-cell signaling through combined increases in transcription and mRNA stability. Transcriptional induction occurs within 6 h of stimulation and is dependent on activation of NF-κB. Subsequently, there is an increase in the stability of the CELF2 mRNA that correlates with a change in CELF2 3′UTR length and contributes to the total signal-induced enhancement of CELF2 expression. Importantly, we uncover dozens of splicing events in cultured T cells whose changes upon stimulation are dependent on CELF2 expression, and provide evidence that CELF2 controls a similar proportion of splicing events during human thymic T-cell development. Taken together, these findings expand the physiologic impact of CELF2 beyond that previously documented in developing neuronal and muscle cells to T-cell development and function, identify unappreciated instances of alternative splicing in the human thymus, and uncover novel mechanisms for CELF2 regulation that may broadly impact CELF2 expression across diverse cell types.

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The Selective Syk Inhibitor P505-15 (PRT062607) Inhibits B Cell Signaling and Function In Vitro and In Vivo and Augments the Activity of Fludarabine in Chronic Lymphocytic Leukemia

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.112.200832 ◽

2012 ◽

Vol 344 (2) ◽

pp. 378-387 ◽

Cited By ~ 30

Author(s):

Stephen E. Spurgeon ◽

Greg Coffey ◽

Luke B. Fletcher ◽

Russell Burke ◽

Jeffrey W. Tyner ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Cell Signaling ◽

B Cell ◽

Lymphocytic Leukemia ◽

B Cell Signaling ◽

Syk Inhibitor ◽

And Function

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Cellular microcompartments constitute general suborganellar functional units in cells

Biological Chemistry ◽

10.1515/hsz-2012-0265 ◽

2013 ◽

Vol 394 (2) ◽

pp. 151-161 ◽

Cited By ~ 15

Author(s):

Joost C.M. Holthuis ◽

Christian Ungermann

Keyword(s):

Plasma Membrane ◽

Cell Signaling ◽

Functional Unit ◽

Redox Status ◽

Eukaryotic Cells ◽

Enzymatic Reactions ◽

Ion Composition ◽

Cellular Dynamics ◽

Remarkable Degree ◽

And Function

Abstract All cells are compartmentalized to facilitate enzymatic reactions or cellular dynamics. In eukaryotic cells, organelles differ in their protein/lipid repertoire, luminal ion composition, pH, and redox status. In addition, organelles contain specialized subcompartments even within the same membrane or within its lumen. Moreover, the bacterial plasma membrane reveals a remarkable degree of organization, which is recapitulated in eukaryotic cells and often linked to cell signaling. Finally, protein-based compartments are also known in the bacterial and eukaryotic cytosol. As the organizing principle of such cellular subcompartments is likely similar, previous definitions like rafts, microdomains, and all kinds of ‘-somes’ fall short as a general denominator to describe such suborganellar structures. Within this review, we will introduce the term cellular microcompartment as a general suborganellar functional unit and discuss its relevance to understand subcellular organization and function.

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