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PC12 cell mutants that possess low- but not high-affinity nerve growth factor receptors neither respond to nor internalize nerve growth factor.
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MedLine Citation:
PMID:  3005338     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Four mutant PC12 pheochromocytoma cell lines that are nerve growth factor (NGF)-nonresponsive (PC12nnr) have been selected from chemically mutagenized cultures by a double selection procedure: failure both to grow neurites in the presence of NGF and to survive in NGF-supplemented serum-free medium. The PC12nnr cells were deficient in all additional NGF responses surveyed: abatement of cell proliferation, changes in glycoprotein composition, induction of ornithine decarboxylase, rapid changes in protein phosphorylation, and cell surface ruffling. However, PC12nnr cells closely resembled non-NGF-treated PC12 cells in most properties tested: cell size and shape; division rate; protein, phosphoprotein, and glycoprotein composition; and cell surface morphology. All four PC12nnr lines differed from PC12 cells in three ways in addition to failure of NGF response: PC12nnr cells failed to internalize bound NGF by the normal, saturable, high-affinity mechanism present in PC12 cells. The PC12nnr cells bound NGF but entirely, or nearly entirely, at low-affinity sites only, whereas PC12 cells possess both high- and low-affinity NGF binding sites. The responses to dibutyryl cyclic AMP that were tested appeared to be enhanced or altered in the PC12nnr cells compared to PC12 cells. Internalization of, and responses to, epidermal growth factor were normal in the PC12nnr cells ruling out a generalized defect in hormonal binding, uptake, or response mechanisms. These findings are consistent with a causal association between the presence of high-affinity NGF receptors and of NGF responsiveness and internalization. A possible relationship is also suggested between regulation of cAMP responses and regulation of NGF responses or NGF receptor affinity.
Authors:
S H Green; R E Rydel; J L Connolly; L A Greene
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of cell biology     Volume:  102     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1986 Mar 
Date Detail:
Created Date:  1986-04-15     Completed Date:  1986-04-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  830-43     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bucladesine / pharmacology
Cell Division
Cell Line
Glycoproteins / analysis
Neoplasm Proteins / analysis
Nerve Growth Factors / metabolism*,  pharmacology
Ornithine Decarboxylase / analysis
Pheochromocytoma / genetics,  metabolism*,  ultrastructure
Phosphoproteins / analysis
Rats
Receptors, Cell Surface / genetics,  metabolism*
Receptors, Nerve Growth Factor
Grant Support
ID/Acronym/Agency:
GM07827/GM/NIGMS NIH HHS; NS06827/NS/NINDS NIH HHS; NS16036/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/Neoplasm Proteins; 0/Nerve Growth Factors; 0/Phosphoproteins; 0/Receptors, Cell Surface; 0/Receptors, Nerve Growth Factor; 362-74-3/Bucladesine; EC 4.1.1.17/Ornithine Decarboxylase
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Cell Biol
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 1 Month: 3 Year: 1986
Volume: 102 Issue: 3
First Page: 830 Last Page: 843
ID: 2114139
Publisher Id: 86140390
PubMed Id: 3005338

PC12 cell mutants that possess low- but not high-affinity nerve growth factor receptors neither respond to nor internalize nerve growth factor


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