Complex and dynamic redistribution of NF-kappaB signaling intermediates in response to T cell receptor stimulation |
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Authors: | Schaefer Brian C Kappler John W Kupfer Abraham Marrack Philippa |
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Institution: | Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. bschaefer@usuhs.mil |
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Abstract: | 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. |
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