RCAN 1 and 3 proteins regulate thymic positive selection

Biochem Biophys Res Commun. 2015 May 1;460(2):295-301. doi: 10.1016/j.bbrc.2015.03.029. Epub 2015 Mar 14.

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.

Keywords: Calcineurin; NFATc; RAF kinase; RCAN1; RCAN3; Thymocyte positive selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Calcium-Binding Proteins
  • Carrier Proteins / immunology
  • Carrier Proteins / physiology*
  • Female
  • Flow Cytometry
  • Humans
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Muscle Proteins / immunology
  • Muscle Proteins / physiology*
  • Real-Time Polymerase Chain Reaction
  • Thymus Gland / embryology
  • Thymus Gland / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DSCR1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • RCAN3 protein, mouse