δ opioid receptors stimulate Akt-dependent phosphorylation of c-jun in T cells

Nahid A. Shahabi, Kathy McAllen, Burt Sharp

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Activation of naive T cells markedly up-regulates the expression of δ opioid receptors (DORs). These receptors are bound by DOR peptides released by T cells, modulating T cell functions such as interleukin-2 production, cellular proliferation, and chemotaxis. Previous studies have shown that DOR agonists [e.g., [D-Ala2-D-Leu5]-enkephalin (DADLE)] modulate T cell antigen receptor signaling through mitogen-activated protein kinases (MAPKs; i.e., extracellular signal-regulated kinases 1 and 2) and that DORs directly induce phosphorylation of activating transcription factor-2 (implicated in cytokine gene transcription) and its association with the MAPK c-jun1 NH2-terminal kinase (JNK). Such observations suggest that DORs may induce the phosphorylation of c-jun. These experiments were performed to test this hypothesis and determine the potential roles of phosphoinositide 3-kinase (PI3K) and Akt (protein kinase B). DADLE (10-10 to 10-6 M) dose-dependently induced c-jun phosphorylation. This was blocked by pertussis toxin and the DOR-specific antagonist naltindole. Fluorescence flow cytometry showed that DADLE significantly stimulated c-jun phosphorylation by T cells. DADLE stimulated phosphorylation of membrane-associated Akt; wortmannin and LY294002 ([2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]), specific inhibitors of PI3K, abolished the DADLE-induced phosphorylation of c-jun. Finally, inhibitors of Akt and JNK blocked DADLE-induced phosphorylation of c-jun. Thus, activated DORs directly stimulate c-jun phosphorylation through a PI3K-dependent pathway in T cells, apparently involving Akt. This implies that DORs activate JNK through a novel pathway dependent on PI3K and Akt, thereby regulating the function of activator protein-1 transcription complexes containing c-jun and other transcription partners.

Original languageEnglish (US)
Pages (from-to)933-939
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume316
Issue number2
DOIs
StatePublished - Feb 1 2006

Fingerprint

Opioid Receptors
Phosphorylation
T-Lymphocytes
1-Phosphatidylinositol 4-Kinase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphotransferases
Activating Transcription Factor 2
Activator Appliances
Peptide T
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Pertussis Toxin
Transcription Factor AP-1
Chemotaxis
T-Cell Antigen Receptor
Mitogen-Activated Protein Kinases
Interleukin-2
Ala(2)-enkephalinamide-met
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

δ opioid receptors stimulate Akt-dependent phosphorylation of c-jun in T cells. / Shahabi, Nahid A.; McAllen, Kathy; Sharp, Burt.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 316, No. 2, 01.02.2006, p. 933-939.

Research output: Contribution to journalArticle

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