NDLI: Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow

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Regulation of morphogenesis and neural differentiation of human mesenchymal stem cells using carbon nanotube sheets

In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity

Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow

RhoA-induced cytoskeletal tension controls adaptive cellular remodeling to mechanical signaling

Encapsulation of angiogenic monocytes using bio-spraying technology

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts

Systematic analysis of embryonic stem cell differentiation in hydrodynamic environments with controlled embryoid body size

A plant virus substrate induces early upregulation of BMP2 for rapid bone formation

Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression

Monitoring of the prostate tumour cells redox state and real-time proliferation by novel biophysical techniques and fluorescent staining

Preparation, characterization, and surface immobilization of native vesicles obtained by mechanical extrusion of mammalian cells

Resolving brain regions using nanostructure initiator mass spectrometry imaging of phospholipids

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Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow

Content Provider	Royal Society of Chemistry (RSC)
Author	Koretzky, Gary A. Kim, Jiyeon Lee, Dooyoung Beste, Michael T. Hammer, Daniel A.
Copyright Year	2012
Abstract	T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.
Starting Page	606
Ending Page	614
Page Count	9
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	4
Issue Number	6
Journal	Integrative Biology
DOI	10.1039/c2ib00002d
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	ISAD Ras T cell Adaptive immune system Diglyceride Guanine nucleotide exchange factor Ras subfamily Integrin Lymphocyte function-associated antigen 1 Stromal cell-derived factor 1 Intercellular adhesion molecule
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow

Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily

Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa (SLP-76) Is Required for Optimal CXCR4-Stimulated T Lymphocyte Firm Arrest to ICAM-1 Under Shear Flow

Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily

Diacylglycerol Kinase ζ Regulates Ras Activation by a Novel Mechanism

ICAM-3 interacts with LFA-1 and regulates the LFA-1/ICAM-1 cell adhesion pathway

The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol (1986)

R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding

The Small GTPase, Rap1, Mediates CD31-induced Integrin Adhesion

Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow

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Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow