|Receptor trafficking via the perinuclear recycling compartment accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase activation.|
|PMID: 14699144 Owner: NLM Status: MEDLINE|
|Most G protein-coupled receptors are internalized after interaction with their respective ligand, a process that subsequently contributes to cell desensitization, receptor endocytosis, trafficking, and finally cell resensitization. Although cellular mechanisms leading to cell desensitization have been widely studied, those responsible for cell resensitization are still poorly understood. We examined here the traffic of the high affinity neurotensin receptor (NT1 receptor) following prolonged exposure to high agonist concentration. Fluorescence and confocal microscopy of Chinese hamster ovary, human neuroblastoma (CHP 212), and murine neuroblastoma (N1E-115) cells expressing green fluorescent protein-tagged NT1 receptor revealed that under prolonged treatment with saturating concentrations of neurotensin (NT) agonist, NT1 receptor and NT transiently accumulated in the perinuclear recycling compartment (PNRC). During this cellular event, cell surface receptors remained markedly depleted as detected by both confocal microscopy and (125)I-NT binding assays. In dividing cells, we observed that following prolonged NT agonist stimulation, NT1 receptors were removed from the PNRC, accumulated in dispersed vesicles inside the cytoplasm, and subsequently reappeared at the cell surface. This NT binding recovery allowed for constant cell sensitization and led to a chronic activation of mitogen-activated protein kinases p42 and p44. Under these conditions, the constant activation of NT1 receptor generates an oncogenic regulation. These observations support the potent role for neuropeptides, such as NT, in cancer progression.|
|Mireille Toy-Miou-Leong; Catherine Llorens Cortes; Alain Beaudet; William Rostène; Patricia Forgez|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-12-29|
|Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Mar|
|Created Date: 2004-03-22 Completed Date: 2004-05-07 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States|
|Languages: eng Pagination: 12636-46 Citation Subset: IM|
|INSERM Unit 482, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France.|
|APA/MLA Format Download EndNote Download BibTex|
Cell Line, Tumor
Cell Membrane / metabolism
Cell Nucleus / metabolism
Cytoplasm / metabolism
Gene Expression Regulation, Neoplastic
Green Fluorescent Proteins
Luminescent Proteins / metabolism
Lysosomes / metabolism
MAP Kinase Signaling System*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Neurotensin / agonists, chemistry*, physiology*
Receptors, Neurotensin / chemistry*
Transferrin / metabolism
Xanthenes / pharmacology
|0/Ligands; 0/Luminescent Proteins; 0/Receptors, Neurotensin; 0/Xanthenes; 11096-37-0/Transferrin; 147336-22-9/Green Fluorescent Proteins; 39379-15-2/Neurotensin; 82354-19-6/Texas red; EC 188.8.131.52/Mitogen-Activated Protein Kinase 1; EC 184.108.40.206/Mitogen-Activated Protein Kinase 3; EC 220.127.116.11/Mitogen-Activated Protein Kinases|
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