Diacylglycerol and protein kinase D localization during T lymphocyte activation.
The serine kinase protein kinase D (PKD) has a cysteine-rich domain (CRD) that binds diacylglycerol (DAG) with high affinity. PKD is cytosolic in unstimulated T cells, but it rapidly polarizes to the immunological synapse in response to antigen/antigen presenting cells (APCs). PKD repositioning is determined by the accumulation of DAG at the immunological synapse and changes in DAG accessibility of the PKD-CRD. Unstimulated T cells are shown to have a uniform distribution of DAG at the plasma membrane, whereas after T cell activation, a gradient of DAG is created with a persistent focus of DAG at the center of the synapse. PKD is only transiently associated with the immune synapse, indicating a fine tuning of PKD responsiveness to DAG by additional regulatory mechanisms. These results reveal the immune synapse as a focal point for DAG and PKD as an immediate and dynamic DAG effector during T cell activation.
Spitaler
Martin
M
University of Dundee/WTB, Dow Street, Dundee DD2 1BE, United Kingdom. m.spitaler@imperial.ac.uk
Emslie
Elisabeth
E
Wood
C David
CD
Cantrell
Doreen
D
D004075:Diglycerides / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D011493:Protein Kinase C / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D004075:Diglycerides; D011948:Receptors, Antigen, T-Cell; C089212:protein kinase D; D011493:Protein Kinase C