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Identification of the cytoskeletal regulatory protein alpha-adducin as a target of T cell receptor signaling.

Authors: Lu, Q  Liu, X  Trama, J  Roti, MA  Go, WY  Ho, SN 
Citation: Lu Q, etal., Mol Immunol. 2004 Jun;41(4):435-47.
Pubmed: (View Article at PubMed) PMID:15163540
DOI: Full-text: DOI:10.1016/j.molimm.2004.03.028

Quiescent T lymphocytes reorganize the actin cytoskeleton subsequent to interaction with antigen presenting cells bearing the appropriate peptide antigen. Although both biochemical and genetic evidence indicate that T cell receptor-dependent cytoskeletal reorganization is critical to T cell activation, the mechanisms that mediate this process remain poorly defined. In this study, the cytoskeletal regulatory protein alpha-adducin was identified as a novel target of TCR signaling in primary T lymphocytes through the biochemical purification of an unknown 120 kDa protein (p120) defined by a fortuitously cross-reactive phospho-sensitive antiserum. The epitope identified by this antiserum defines a previously unrecognized site of phosphorylation localized to amino acids 590-620. Both TCR cross-linking and exposure to phorbol ester resulted in the phosphorylation-dependent elimination of this epitope. However, while phorbol ester induced rapid phosphorylation of both the phospho-sensitive epitope and the functionally defined major protein kinase C site present near the carboxy-terminus (serine 724) of alpha-adducin, only the phospho-sensitive epitope was modified upon activation through the TCR. Moreover, inhibition of actin polymerization by cytochalasin D blocked this modification. Of particular importance, alpha-adducin was not expressed in T cell lines, was completely down-regulated in primary T cells within 24h of activation and was reduced in quiescent memory T cells. These results suggest a model in which reorganization of the unique cytoskeletal network that defines a primary quiescent T lymphocyte is mediated in part through the TCR-dependent modification and subsequent down-regulation of alpha-adducin, thereby resulting in a cytoskeletal architecture compatible with T cell effector and memory functions.

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RGD Object Information
RGD ID: 1624956
Created: 2007-05-14
Species: All species
Last Modified: 2007-05-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.