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Phosphorylation of activating transcription factor in murine splenocytes through delta opioid receptors

N A Shahabi1, K McAllen, B M Sharp

  • 1Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Cellular Immunology
|May 16, 2003
PubMed

Insights

Delta opioid receptors (DORs) activate the c-Jun NH2-terminal kinase (JNK) pathway, independent of T-cell receptor (TCR) signaling. This DOR-mediated JNK activation suggests a novel mechanism for modulating immune cell responses.

Area of Science:

  • Immunology
  • Neuroscience
  • Cell Signaling

Background:

  • Delta opioid receptors (DORs) are known to modulate T-cell receptor (TCR) signaling via mitogen-activated protein kinases (MAPKs), specifically ERKs 1 and 2.
  • The precise mechanisms by which DORs influence other MAPK pathways, such as c-Jun NH2-terminal kinase (JNK), remain less understood.

Purpose of the Study:

  • To investigate whether a DOR agonist, [D-Ala(2)-D-Leu(5)]enkephalin (DADLE), directly affects the phosphorylation of activating transcription factor-2 (ATF-2) and its interaction with JNK.
  • To determine if DOR activation can independently modulate JNK signaling in lymphocytes.

Main Methods:

  • Murine splenocytes were stimulated with anti-CD3 to induce DOR expression.
  • Quiescent cells were treated with DADLE, and subsequent phosphorylation of ATF-2 and its association with JNK were analyzed using immunoprecipitation.
  • The effect of naltrindole, a specific DOR antagonist, was assessed.

Main Results:

  • DADLE treatment dose-dependently induced maximal phosphorylation of ATF-2 within 5-10 minutes, an effect abolished by naltrindole.
  • Immunoprecipitation revealed that DADLE stimulated the phosphorylation of both 59kDa and 71kDa ATF-2 bands.
  • The 71kDa ATF-2 band was selectively immunoprecipitated by anti-JNK, indicating DADLE stimulates ATF-2 phosphorylation and its association with JNK.

Conclusions:

  • Lymphocyte DORs can activate the JNK pathway through TCR-independent stimulation.
  • These findings suggest DORs play a role in modulating immune cell signaling by influencing both TCR-dependent (ERK) and TCR-independent (JNK) MAPK pathways.

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