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- Publisher Website: 10.1074/jbc.M111.296798
- Scopus: eid_2-s2.0-84862908520
- PMID: 22110135
- WOS: WOS:000299170300042
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Article: Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21 cip1 signaling
Title | Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21 cip1 signaling |
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Authors | |
Issue Date | 2012 |
Citation | Journal of Biological Chemistry, 2012, v. 287, n. 2, p. 1261-1268 How to Cite? |
Abstract | The maintenance of T cell memory is critical for the development of rapid recall responses to pathogens, but may also have the undesired side effect of clonal expansion of T effector memory (T EM) cells in chronic autoimmune diseases. The mechanisms by which lineage differentiation of T cells is controlled have been investigated, but are not completely understood. Our previous work demonstrated a role of the voltage-gated potassium channel Kv1.3 in effector T cell function in autoimmune disease. In the present study, we have identified a mechanism by which Kv1.3 regulates the conversion of T central memory cells (T CM) into T EM. Using a lentiviral-dominant negative approach, we show that loss of function of Kv1.3 mediates reversion of T EMinto T CM, via a delay in cell cycle progression at the G2/M stage. The inhibition of Kv1.3 signaling caused an up-regulation of SMAD3 phosphorylation and induction of nuclear p21 cip1 with resulting suppression of Cdk1 and cyclin B1. These data highlight a novel role for Kv1.3 in T cell differentiation and memory responses, and provide further support for the therapeutic potential of Kv1.3 specific channel blockers in T EM-mediated autoimmune diseases. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. |
Persistent Identifier | http://hdl.handle.net/10722/237107 |
ISSN | 2020 Impact Factor: 5.157 2023 SCImago Journal Rankings: 1.766 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Hu, Lina | - |
dc.contributor.author | Gocke, Anne R. | - |
dc.contributor.author | Knapp, Edward | - |
dc.contributor.author | Rosenzweig, Jason M. | - |
dc.contributor.author | Grishkan, Inna V. | - |
dc.contributor.author | Baxi, Emily G. | - |
dc.contributor.author | Zhang, Hao | - |
dc.contributor.author | Margolick, Joseph B. | - |
dc.contributor.author | Whartenby, Katharine A. | - |
dc.contributor.author | Calabresi, Peter A. | - |
dc.date.accessioned | 2016-12-20T06:48:38Z | - |
dc.date.available | 2016-12-20T06:48:38Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2012, v. 287, n. 2, p. 1261-1268 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10722/237107 | - |
dc.description.abstract | The maintenance of T cell memory is critical for the development of rapid recall responses to pathogens, but may also have the undesired side effect of clonal expansion of T effector memory (T EM) cells in chronic autoimmune diseases. The mechanisms by which lineage differentiation of T cells is controlled have been investigated, but are not completely understood. Our previous work demonstrated a role of the voltage-gated potassium channel Kv1.3 in effector T cell function in autoimmune disease. In the present study, we have identified a mechanism by which Kv1.3 regulates the conversion of T central memory cells (T CM) into T EM. Using a lentiviral-dominant negative approach, we show that loss of function of Kv1.3 mediates reversion of T EMinto T CM, via a delay in cell cycle progression at the G2/M stage. The inhibition of Kv1.3 signaling caused an up-regulation of SMAD3 phosphorylation and induction of nuclear p21 cip1 with resulting suppression of Cdk1 and cyclin B1. These data highlight a novel role for Kv1.3 in T cell differentiation and memory responses, and provide further support for the therapeutic potential of Kv1.3 specific channel blockers in T EM-mediated autoimmune diseases. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Biological Chemistry | - |
dc.title | Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21 cip1 signaling | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1074/jbc.M111.296798 | - |
dc.identifier.pmid | 22110135 | - |
dc.identifier.scopus | eid_2-s2.0-84862908520 | - |
dc.identifier.volume | 287 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 1261 | - |
dc.identifier.epage | 1268 | - |
dc.identifier.eissn | 1083-351X | - |
dc.identifier.isi | WOS:000299170300042 | - |
dc.identifier.issnl | 0021-9258 | - |