T lymphocyte activation initiates the degradation of the CD62L encoding mRNA and increases the transcription of the corresponding gene

Immunol Lett. 2004 Jun 15;94(1-2):115-22. doi: 10.1016/j.imlet.2004.04.009.

Abstract

Following T-cell activation, CD62L, a member of the selectin family of cell adhesion molecules, is proteolytically cleaved by a constitutive endoprotease and subsequently re-expressed. To define whether the cleavage regulates CD62L gene transcription, we have analyzed the outcome of T-cell activation on the level of CD62L gene transcription and mRNA stability. Here, we report that CD62L shedding correlates with the concomitant upregulation of CD62L gene transcription and the rapid degradation of the corresponding mRNA. Novel protein synthesis is not required for CD62L gene upregulation, mRNA degradation or protein shedding. The three events are insensitive to cyclosporin A (CSA) and, thus, do not depend on the calcineurin signaling pathway. Activation of T cells in presence of a metallo-protease inhibitor, that protects CD62L shedding, does not prevent CD62L gene upregulation or mRNA degradation. In contrast induction of CD62L shedding by the chemically-induced dissociation of calmodulin from the CD62L cytosolic tail, in absence of T-cell activation, has no consequences on the levels of CD62L gene transcription or mRNA accumulation. These data demonstrate that the transcriptional and post-transcriptional events are exclusively regulated by T-cell activation and not by the CD62L density on cell membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcineurin / metabolism
  • Concanavalin A / pharmacology
  • Cyclosporine / pharmacology
  • L-Selectin / genetics*
  • L-Selectin / metabolism
  • Lymphocyte Activation / genetics*
  • Mice
  • RNA Stability / genetics*
  • RNA, Messenger / metabolism*
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transcriptional Activation*

Substances

  • RNA, Messenger
  • Concanavalin A
  • L-Selectin
  • Cyclosporine
  • Calcineurin