Stimulatory and suppressive signal transduction regulates vasoactive intestinal peptide receptor-1 (VPAC-1) in

Emilie E Vomhof-DeKrey1, Glenn Paul Dorsam1

  • 1Department of Chemistry and Molecular Biology, The Center for Protease Research, North Dakota State University, Room 320 IACC Building, 1320 Albrecht Boulevard, Fargo, ND 58105, USA.

Insights

This study reveals that JNK kinases suppress Vasoactive intestinal peptide receptor-1 (VPAC-1) mRNA levels in T cells upon activation. Other signaling pathways, like PKC and ERK, stimulate VPAC-1 in the absence of T cell signaling.

Area of Science:

  • Immunology
  • Cell Signaling

Background:

  • Vasoactive intestinal peptide receptor-1 (VPAC-1) is a G-protein coupled receptor expressed on T cells.
  • VPAC-1 is downregulated upon T cell activation, but the underlying signaling pathways remain unclear.

Purpose of the Study:

  • To investigate the signaling pathways regulating VPAC-1 expression in murine CD4 T cells.
  • To identify molecules involved in the downregulation of VPAC-1 during T cell activation.

Main Methods:

  • Murine splenic CD4 T cells were treated with pharmacological inhibitors.
  • Cells were stimulated with anti-CD3 antibody for 24 hours.
  • VPAC-1 mRNA levels were quantified using qPCR.

Main Results:

  • JNK kinases, downstream of Zap70, suppress VPAC-1 mRNA levels following anti-CD3 stimulation.
  • Inhibitors of PKC, ERK, p38, Zap70, and Rac1 indicated a stimulatory role in VPAC-1 regulation without T cell signaling.

Conclusions:

  • JNK signaling pathway plays a suppressive role in VPAC-1 regulation post-T cell activation.
  • Understanding VPAC-1 regulation offers insights into its role in inflammatory and autoimmune diseases.