Itk is a Critical Regulator of Spatiotemporal Localization at the Immunological Synapse

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Title: Itk is a Critical Regulator of Spatiotemporal Localization at the Immunological Synapse
Author: Singleton, Kentner Leroy
Abstract: The activation of T cells by antigen presenting cells (APCs ) is an important step in the initiation of the adaptive immune response . Itk , a member of the Tec family of non -receptor protein tyrosine kinases , is important for T cell activation – Itk - / - CD4+ T cells are hyporesponsive , displaying decreased calcium flux , proliferation , and IL2 production compared to wildtype T cells . The mechanism by which Itk mediates this effect is not fully elucidated . Here we show that Itk is a key regulator of spatiotemporal localization of receptors and proximal signaling intermediates at the T cell / APC interface . As part of this organizational regulation , we found that Itk , through the recruitment of SLAT , mediates activation of Cdc42 at the center of the interface , which is critically required for actin polymerization . We show that targeting activated Cdc42 to the center of the interface restores actin polymerization in the Itk - / - T cell while the addition of constitutively active Cdc42 to the entirety of the interface cannot . These results provide beginnings of a mechanistic explanation of how Itk both regulates the actin cytoskeleton and acts to amplify T cell signaling . These results further demonstrate that control of protein localization at the immunological synapse can be the critical determinant in protein function and that the center of the interface is a site of active signaling .
URI: http : / /hdl .handle .net /2152 .5 /765
Date: 2010-05-14

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Itk is a Critical Regulator of Spatiotemporal Localization at the Immunological Synapse. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /765 .

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