Document Detail

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.
MedLine Citation:
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-12-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Mar 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  12636-46     Citation Subset:  IM    
INSERM Unit 482, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France.
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MeSH Terms
Biological Transport
CHO Cells
Cell Differentiation
Cell Line, Tumor
Cell Membrane / metabolism
Cell Nucleus / metabolism
Cytoplasm / metabolism
Disease Progression
Enzyme Activation
Gene Expression Regulation, Neoplastic
Green Fluorescent Proteins
Luminescent Proteins / metabolism
Lysosomes / metabolism
MAP Kinase Signaling System*
Microscopy, Confocal
Microscopy, Fluorescence
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Neurotensin / agonists,  chemistry*,  physiology*
Protein Binding
Receptors, Neurotensin / chemistry*
Time Factors
Transferrin / metabolism
Xanthenes / pharmacology
Reg. No./Substance:
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 Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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