RCAN 1 and 3 proteins regulate thymic positive selection

Eva Serrano-Candelas, German R Aleman-Muench, Sonia Sole-Sanchez, Anna Aubareda, Sergio Martinez-Hoyer, Jaume Adan, Alvaro Aranguren-Ibanez, Melanie A Pritchard, Gloria Soldevila, Merce Perez-Riba

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Abstract

Cooperation between calcineurin (CN)-NFATc and RAF-MEK-ERK signaling pathways is essential in thymocyte positive selection. It is known that the Regulators of Calcineurin (RCAN) proteins can act either facilitating or suppressing CN-dependent signaling events. Here, we show that RCAN genes are expressed in lymphoid tissues, and address the role of RCAN proteins in T cell development. Overexpression of human RCAN3 and RCAN1 can modulate T cell development by increasing positive selection-related surface markers, as well as the Erk(hi) competence state in double positive thymocytes, a characteristic molecular signature of positive selection, without affecting CN activity. We also found that RCAN1/3 interact with RAF kinases and CN in a non-exclusive manner. Our data suggests that the balance of RCAN interactions with CN and/or RAF kinases may influence T cell positive selection.
Original languageEnglish
Pages (from-to)295-301
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume460
Issue number2
DOIs
Publication statusPublished - 2015

Keywords

  • Calcineurin
  • NFATc
  • RAF kinase
  • RCAN1
  • RCAN3
  • Thymocyte positive selection

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