Electronic Resource
Signal Transducer and Activator of Transcription 3 Activation by the δ-Opioid Receptor via Gα14 Involves Multiple Intermediates
| العنوان: | Signal Transducer and Activator of Transcription 3 Activation by the δ-Opioid Receptor via Gα14 Involves Multiple Intermediates |
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| المؤلفون: | Lo, Kin H., Wong, Yung Hou |
| بيانات النشر: | 2004 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | The hematopoietic-specific Galpha(14) links a variety of G protein-coupled receptors to phospholipase Cbeta (PLCbeta) stimulation. Recent studies reveal that several Galpha subunits are capable of activating signal transducer and activator of transcription ( STAT) proteins. In the present study, we investigated the mechanism by which Galpha(14) mediates receptor-induced stimulation of STAT3. In human embryonic kidney 293 cells, coexpression of Galpha(14) with delta-opioid receptor supported [D-Pen(2), D-Pen(5)]enkephalin (DPDPE)-induced STAT3 phosphorylations at both Tyr(705) and Ser(727) in a pertussis toxin-insensitive manner. The constitutively active Galpha(14)QL mutant also induced STAT3 phosphorylations at these sites and promoted STAT3-dependent luciferase activity. Requirements for PLCbeta, protein kinase C (PKC), and calmodulin-dependent kinase II ( CaMKII) in Galpha(14) QL-induced STAT3 activation were demonstrated by their respective inhibitors as well as by coexpression of their dominant-negative mutants. Inhibition of c-Src and Janus kinase 2 and 3 activities abolished STAT3 activation induced by Galpha(14)QL, but no physical association between Galpha(14)QL and c-Src could be detected by coimmunoprecipitation. Various intermediates along the extracellular signal-regulated kinase signaling cascade were apparently required for Galpha(14)QL-induced STAT3 activation; they included Ras/Rac1, Raf-1, and mitogen-activated protein kinase kinase-1/2. In contrast, functional blockade of c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol-3 kinase had no effect on Galpha(14)QL-induced responses. PLCbeta, PKC, and CaMKII were shown to be involved in Galpha(14) QL-mediated c-Src phosphorylation. Similar results were obtained with human erythro-leukemia cells upon DPDPE treatment. These results demonstrate for the first time that Galpha(14) activation can lead to STAT3 stimulation via a complex signaling network involving multiple |
| مصطلحات الفهرس: | Cells, Cultured, DNA-Binding Proteins: genetics, DNA-Binding Proteins: metabolism, Enkephalin, D-Penicillamine (2,5)-: pharmacology, GTP-Binding Protein alpha Subunits, Gq-G11, Heterotrimeric GTP-Binding Proteins: physiology, Humans, Isoenzymes: physiology, Janus Kinase 2, Mutation, Phosphatidylinositol 3-Kinases: metabolism, Phospholipase C beta, Protein-Tyrosine Kinases: metabolism, Proto-Oncogene Proteins, Receptors, Opioid, delta: physiology, STAT3 Transcription Factor, Signal Transduction: physiology, Time Factors, Trans-Activators: genetics, Trans-Activators: metabolism, Transcriptional Activation: physiology, Transfection, Type C Phospholipases: physiology, Rac1 GTP-Binding Protein: metabolism, Ras Proteins: metabolism, Article |
| URL: | |
| الاتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| Other Numbers: | HNK oai:repository.ust.hk:1783.1-30775 Molecular Pharmacology, v. 65, (6), June 2004, p. 1487-1439 0026-895X 1521-0111 https://doi.org/10.1124/mol.65.6.1427 895578456 |
| المصدر المساهم: | HONG KONG UNIV OF SCI & TECH, THE From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn895578456 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |