Phosphorylation of activating transcription factor in murine splenocytes through delta opioid receptors.
Delta opioid receptors (DORs) modulate TCR signaling through the mitogen-activated protein kinases (MAPKs), ERKs 1 and 2. These studies determined whether a DOR agonist alone ([D-Ala(2)-D-Leu(5)]enkephalin; DADLE) affects phosphorylation of the activating transcription factor (ATF-2) and its interaction with the MAPK, c-Jun NH(2)-terminal kinase (JNK). DOR expression was induced on murine splenocytes by anti-CD3 and then quiescent cells were treated with DADLE. DADLE, itself, dose-dependently induced maximal phosphorylation of ATF-2 within 5-10min; naltrindole, a specific antagonist, abolished this. Anti-ATF-2 immunoprecipitates from control and DADLE-treated splenocytes showed a dominant 59kDa phosphorylated band and a 71kDa band. DADLE stimulated phosphorylation of both bands, although the 71kDa band was selectively immunoprecipitated by anti-JNK. Thus, DADLE stimulated phosphorylation of 71kDa ATF-2 and its association with JNK, suggesting that JNK is activated through DORs. Along with previous observations, these studies suggest that lymphocyte DORs can affect the activation of MAPKs by TCR-independent stimulation (e.g., JNK) or indirectly by modulating TCR-dependent stimulation (e.g., ERK).
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
N A
NA
Shahabi
K
K
McAllen
B M
BM
Sharp
D051698:Activating Transcription Factor 2; D000818:Animals; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology / Q000378:metabolism*; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010766:Phosphorylation; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D014157:Transcription Factors; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C055382:naltrindole