| http://purl.uniprot.org/citations/22546945 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22546945 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.org/dc/terms/identifier | "doi:10.1039/c2ib00002d"xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/author | "Kim J."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/author | "Lee D."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/author | "Koretzky G.A."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/author | "Hammer D.A."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/author | "Beste M.T."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/name | "Integr Biol (Camb)"xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/pages | "606-614"xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/title | "Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow."xsd:string |
| http://purl.uniprot.org/citations/22546945 | http://purl.uniprot.org/core/volume | "4"xsd:string |
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