| Expression of a G protein subunit, alpha i-1, in Balb/c 3T3 cells leads to agonist-specific changes in growth regulation. | |
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MedLine Citation:
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PMID: 1939086 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cellular receptors for many hormones, neurotransmitters, and growth factors are coupled to intracellular effector enzymes or ion channels through a set of heterotrimeric G proteins. In order to determine whether isoforms of G protein alpha subunits contribute differentially to mitogenic responses, we introduced an alpha subunit isoform, alpha i-1, into Balb/c 3T3 cells that normally lack this subtype. Balb/c 3T3 cells transfected with a plasmid containing cDNA encoding alpha i-1 expressed the alpha i-1 protein as judged both by the appearance of immunoreactive alpha i-1 protein on Western blots and by two-dimensional analysis of the proteins [32P]ADP-ribosylated by pertussis toxin. The amount of alpha i-1 expressed is less than the amount of alpha subunits endogenously present in these cells. Expression of alpha i-1 in the transfected cells slightly blunts stimulation of adenylylcyclase by GTP, guanosine 5'-3-O-(thio)triphosphate, or forskolin, but has no major effect on the ability of thrombin to inhibit the enzyme. In contrast, the expression of alpha i-1 has significant effects on cell growth and on the mitogenic response to thrombin. The alpha i-1-transfected cells have a doubling time that is twice as long as control cells transfected with the same plasmid without a cDNA insert. Despite their slower growth, thymidine incorporation in response to thrombin is greater in transfected than in control cells. Thrombin-stimulated DNA synthesis is sensitive to inhibition by pertussis toxin and is 5-fold more sensitive to inhibition by pertussis toxin in transfected cells than in control cells. The changes are receptor-specific since the mitogenic response to platelet-derived growth factor is indistinguishable between control and transfected cells. These studies suggest that the alpha i subunit composition of the cell may have profound effects on its growth and its response to stimulation through a specific cell surface receptor. |
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Authors:
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Z Cui; M Zubiaur; D B Bloch; T Michel; J G Seidman; E J Neer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 266 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1991 Oct |
Date Detail:
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Created Date: 1991-12-02 Completed Date: 1991-12-02 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 20276-82 Citation Subset: IM |
Affiliation:
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Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells
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drug effects Adenylate Cyclase / metabolism Animals Blotting, Western Cell Cycle / drug effects DNA / biosynthesis, drug effects, genetics Electrophoresis, Gel, Two-Dimensional GTP-Binding Proteins / genetics*, metabolism Genetic Vectors Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology Mice Mice, Inbred BALB C Mitogens* Pertussis Toxin Platelet-Derived Growth Factor / pharmacology Thrombin / pharmacology Transfection Virulence Factors, Bordetella / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA 46361/CA/NCI NIH HHS; GM 36295/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Mitogens; 0/Platelet-Derived Growth Factor; 0/Virulence Factors, Bordetella; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 9007-49-2/DNA; EC 2.4.2.31/Pertussis Toxin; EC 3.4.21.5/Thrombin; EC 3.6.1.-/GTP-Binding Proteins; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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