Complex and dynamic redistribution of NF-kappaB signaling intermediates in response to T cell receptor stimulation.
The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T cell receptor (TCR) enrichment that forms at a T cell/antigen-presenting cell (APC) junction in response to antigen stimulation. We demonstrate that there is a surprisingly complex relocalization process that brings PKC and Bcl10, two intermediates in TCR activation of NF-kappaB, to the cytoplasmic face of the c-SMAC. TCR activation causes enrichment of PKC at the c-SMAC, followed by Bcl10 relocalization to punctate cytoplasmic structures, often at sites distant from the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming enriched at the c-SMAC. TCR activation of NF-kappaB therefore involves the dynamic relocalization of multiple signaling intermediates, with distinct phases proximal to and distant from the c-SMAC.
Schaefer
Brian C
BC
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. bschaefer@usuhs.mil
Kappler
John W
JW
Kupfer
Abraham
A
Marrack
Philippa
P
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002352:Carrier Proteins / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D002352:Carrier Proteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell